Bio

PROF. ANASTASIA NKATHA GUANTAI

PROFESSOR OF PHARMACOLOGY AND THERAPEUTICS

DEPARTMENT OF PHARMACOLOGY AND PHARMACOGNOSY UNIVERSITY OF NAIROBI

Publications


2016

Ngayo1, MO, Okalebo2 FA, Bulimo3 WD, Mwachari C, Guantai2 AN, Oluka2 M.  2016.  Impact of First Line Antiretroviral Therapy on Clinical Outcomes Among HIV-1 Infected Adults Attending One of the Largest HIV Care and Treatment Program in Nairobi Kenya. 1000615Journal of AIDS & Clinical Research. 7(10):7-10.
Yarmoshuk, AN, Gauntai A, Mwangu M, Cole D, Zarowsky C.  2016.  Resilient and responsive Global Health partnerships of East African universities in a changing world, 20 March. Fourth Global Symposium on Health Systems Research. resilient_and_responsive_global_health_partnerships_of_east_african.pdf

2015

Makori, J, Ambetsa M, Sinei KA, Osanjo GO, Guantai AN, McClelland S, Oluka MN, Okalebo FA.  2015.  Patterns and Risk Factors for Alanine Aminotransferase Elevation among HIV Patients on Nevirapine Regimens. African Journal of Pharmacology and Therapeutics. 4(2):59-66.patterns_and_risk_factors_for_alanine_aminotransferase_elevation_among_hiv_patients_on_nevirapine_regimens.pdf
Malele1, CN, Lang’at-Thoruwa CC, Guantai2 AN, Chhabra SC.  2015.  A new pterocarpan from the leaves of Abrus precatorius L.. Academic journals. 9(27):749-754,.a_new_pterocarpan_from_the_leaves_of_abrus_precatorius.pdf
IN, C, FA O, AN G, S1 K.  2015.  A Quality Control of Hypoglycemic Herbal Preparations in Nairobi, Kenya. Journal of Pharmacognosy and Phytochemistry. 3(4):16-21.a_quality_control_of_hypoglycemic_herbal_preparations_in_nairobi.pdf
Oluka, MN, Okalebo FA, Guantai AN, McClelland S, Graham SM.  2015.  Cytochrome P450 2B6 genetic variants are associated with plasma nevirapine levels and clinical response in HIV-1 infected Kenyan women: a prospective cohort study. AIDS Research and Therapy. 12(10):DOI10.1186/s12981-015-0052-0. Abstractoluka_et_al_2015.pdfWebsite

Background: Polymorphisms in cytochrome P450 2B6 (CYP2B6) affect the steady state plasma concentration of nevirapine. CYP2B6 516G>T and 983T>C are common in African populations, but data on their influence on plasma nevirapine concentration and clinical response in African women are limited. We investigated the impact of CYP 516G>T and 983T>C on plasma nevirapine concentration and clinical outcomes in a prospective cohort study of HIV-infected Kenyan women.
Methods: Study subjects were 66 HIV-1-seropositive women taking nevirapine-based antiretroviral therapy. Plasma collected at week 12 was analyzed for nevirapine concentration by high performance liquid chromatography. Baseline samples were genotyped for CYP2B6 516G>T and 983T>C single nucleotide polymorphisms by real-time polymerase chain reaction. CD4 cell count, plasma viral load, and genotypic drug resistance in plasma and genital secretions were assessed at baseline and during follow up. We evaluated the effect of each genotype on plasma nevirapine concentration at week 12 and on change in CD4 cell count at months 3, 6 and 12. Associations between plasma nevirapine concentration and clinical outcomes were analyzed by logistic or linear regression.
Results: Women with CYP2B6 516TT genotype (n=9) had higher mean nevirapine plasma levels (14.33 μg/mL) compared to those with heterozygous 516GT (9.18 μg/mL; n=25) and wild- type 516GG (7.95 μg/mL; n=32) genotypes (P=0.01). Women heterozygous for the CYP2B6 983TC genotype (n=13) had higher mean nevirapine plasma levels (12.94 μg/mL), compared to women with the homozygous 983TT (8.35 μg/mL; n=53) genotype (P=0.007). In Generalized Estimating Equation analysis, plasma nevirapine levels predicted greater change in CD4 cell count after ART initiation (adjusted beta 119.4 cells/μL, 95% CI, 27.3–211.5 cells/μL, P=0.01). The CYP2B6 983TT genotype also predicted greater change in CD4 cell count (adjusted beta 68.6 cells/μL, 95% CI, 3.9–133.4 cells/μL, P=0.04). We found no associations between CYP2B6 genotypes and virologic response or toxicity.
Conclusions: CYP2B6 516G>T and CYP2B6 983T>C genotypes were strongly associated with plasma nevirapine concentration, which predicted immunologic response in women on nevirapine-based antiretroviral therapy. These data support continued work on the potential utility of human genetic testing to inform nevirapine dosage optimization for individual patients.
Keywords: CYP2B6, Pharmacogenetics, Nevirapine, HIV infection, Antiretroviral therapy, Women

2014

Ebeshi, BU, Bolaji2 OO, Oluka3 M, Edebi1 VN, Soyinka2 JO, Guantai3 A.  2014.  Simple Reversed-Phase High Performance Liquid Chromatographic Estimation of the Antiretroviral Agent Efavirenz from Human Plasma. British Journal of Pharmaceutical Research. 4(1):145-157.simple_reversed-phase_high_performance.pdf

2013

Wata, DE, Osanjo G, Oluka M, Guantai A.  2013.  Predictors of Breast Cancer Treatment Outcomes in Kenyan Women. African Journal of Pharmacology and Therapeutics. 2(4):109-115.predictors_of_breast_cancer_treatment_outcomes_in_kenyan_women.pdf

2012

Nwaka, S, Ochem A, Besson D, Ramirez B, Fakorede F, Botros S, Inyang U, Mgone C, Adae-Mensah I, Konde V, Nyasse B, Okole B, Guantai A, Loots G, Atadja P, Ndumbe P, Sanou I, Olesen O, Ridley R, Ilunga T.  2012.  Analysis of pan-African Centres of excellence in health innovation highlights opportunities and challenges for local innovation and financing in the continent. 12. 11(12):2-15.: BMC International Health and Human Rightsanalysis_of_pan-african_centres_of_excellence_in_health_innovation_highlights_opportunities_and_challenges_for_local_innovation_and_in.pdf
Tarkang, PA, Guantai AN;, Tsabang N;, Agbor GA;, Okalebo FA;, Rukunga GM;.  2012.  Indigenous Knowledge and folk use of a polyherbal antimalarial by the Bayang Community, South West Region of Cameroon. Abstract

Nefang is a polyherbal preparation constituted of the leavesof six plants and the bark of one of these,used traditionally for the treatment of malaria by the Bayang community, South West Region of Cameroon. Since no ethnopharmacological survey has been carried out on this preparation, this study aims at obtaining indigenous and folkloric information on the optimal methods for harvesting of constituent plants, preparation and administration of Nefang in the treatment of malaria. The study design was an exploratory survey.Semi-structured questionnaires were administered randomly to 20 respondents after obtaining their informed consent with the assistance of a medical practitioner. Review of literature of constituent plants was also undertaken. This study revealed that the respondents had a good knowledge of malaria and its causes. Various compositions for the preparation by decoction was obtained and administration was ascertained to be by oral route or by enema. The brief scientific review also validated the pharmacological actions of the constituent plants. The diverse indigenous knowledge and folk use of this preparation in the treatment of malaria are a pre-requisite for theoptimization of its compositionfor efficacy and pharmacological screening

2011

Kibwage, IO, Okalebo FA, Guantai AN, Karume DW, K. M, Maitai CK.  2011.  Pharmacological screening of extracts of Clematis brachiata THUNBERG (RANUNCULACEAE).

2010

N, PROFGUANTAIA, N PROFGUANTAIA, N PROFGUANTAIA, N PROFGUANTAIA.  2010.  Validation of a competitive chloramiphenicol enzyme linked immunosorbent assay for determination of residues in Ovine tissues. 12 East and Central African Journal of Pharmaceutical Sciences. : G. A MURILLA, J.O WESONGA, T. FODDEY, S. CROOKS, A.N GUANTAI, W,M KARANJA, T.E MAITHO
N, PROFGUANTAIA.  2010.  Comparative tolerability and efficacy of stavudine 30 mg versus stavudine 40 mg in patients on combination antiretroviral therapy in Kenya. ournal of AIDS and HIV Research Vol. 2(2) pp. 024-031. : Monicah Wanjiru Karara, Faith Apolot Okalebo, Margaret Ng Abstract

Stavudine- containing regimens are currently the most widely used first-line anti-HIV treatment option in Kenya. This study compared the efficacy and tolerability of stavudine at two dose levels in patients attending a HIV Comprehensive Care Centre in Kenya. Data were collected retrospectively from the records of 810 adult patients. Fewer stavudine related adverse effects were seen in patients 60 kg treated with 30 mg stavudine compared to those who received 40 mg (4.2 vs 16.7%, p <0.001). Patients < 60 kg were more likely to experience drug toxicity than those 60 kg when given 30 mg stavudine (12.8 vs 4.2%, p < 0.001). Occurrence of any adverse drug reaction was significantly associated with severe immunosuppression (HR =1.45, Cl: 0.86 - 2.45, p < 0.001), co-morbidities (HR = 2.16, Cl: 1.06 - 4.38, p < 0.001) and treatment with isoniazid (HR = 2.07, Cl: 1.09 - 3.96, p < 0.001). The onset of drug related toxicities was principally in the first year of commencing therapy. Similar immunologic outcomes were demonstrated across all the treatment groups with median CD4 cell counts after 12 months of treatment more than doubling for patients in all the study cohorts. The findings support the use of combination antiretroviral therapy regimens containing low dose stavudine in Kenya. Key words: Low -dose stavudine, combination antiretroviral therapy, HIV, stavudine tolerability.

2009

N, PROFGUANTAIA, N PROFGUANTAIA.  2009.  DEVELOPMEMENT OF A HPLC-MS/MS METHOD FOR THE ANALYSIS OF HYDROZINOCURCUMIN IN PLASMA. 12 East and Central African Journal of Pharmaceutical Sciences. : FA Okalebol , L Wiesner, AN Guantai, K Chibale, P Smith Abstract

The natural product curcumin has a wide range of useful biological effects. However its use in humans is limited due to its short half-life, rapid metabolism and poor oral bioavailability. It is metabolized by sequential reduction of carbon-carbon double two carbonyl groups. To overcome these limitations, a hydrazide derivative of curcumin was synthesized to improve its water solubility and reduce its rate of metabolism. The objective of study was, therefore, to develop a method for the analysis of hydrazinocureumin in murinc blood. This method will be eventually used to evaluate the pharmokinetic profile of hydrazinocurcumin in mice. Method: LC/MS/MS was selected as the analytic method because its high sensitivity allowed for sampling of small volumes of blood from mice. The optimal chromatographic and mass spectrometry conditions were determined by trial arid error. The column performance was monitored by measuring retention time, peak symmetry factor. A calibration curve was generated by using standard solutions with concentrations ranging from 0.78 - 10 rig/ml. The method was validated by determining the recovery, limit of detection, accuracy, linearity and intraday precision. The optimal method for extracting hydrazinocurcumin from biological fluids was determined by spiking human blood and plasma and extraction was done by solvent extraction from a spotted filter paper and liquid-liquid extraction. Instrumentation: The samples were assayed using an Agilent LC/MS/MS 3200Q Trap system (1100 series, USA) in the positive ionization mode. HPLC separation was done using an Agilent 1200 system (Agilent Technologies, Japan) interfaced with the MS/MS system. Ionization was done by electron spray ionization with a collision energy was 33eV. Chromatograms were integrated using Analyst version 1.4 software. Weighted linear regression was used to generate calibration curves from standard solutions. Results: The optimal conditions for HPLC separation was a mobile phase of 0.1% formic acid in acetonitrile: acetonitrile (1:1) with an isocratic flow rate of 0.3m1/minute and run time of 2 minutes. The analytical column was a 50 by 2.0 mm Pheromex C18 column with a particle size of 5 microns. The injection volume was 1 Out The hydrazinocurcumin formed molecular ion at M+H+ m/z 365.2 and two metastable ions at m/z 351 and m/z. 349.2. The transition monitored was m/z 365.2 to 349.2 at unit resolution and a dwelling time of 150 milliseconds. The retention time was 1.11 minutes. The optimal method of extraction was liquid-liquid extraction using 250 ul of ethyl acetate from 10 ul of whole blood in 50 ul of buffer at pH 10. The filter paper method of extraction was found to give erratic results. The calibration curve was linear over the concentration range of 10n/m1 to 0.5 ng/ml of hydrazinocurmin in whole human blood. Conclusion: The precision, accuracy, recovery and applicability were found to be adequate for pharmacokinetic studies in mice.

2008

N, PROFGUANTAIA.  2008.  The in vitro anti-plasmodial and in vivo anti-malarial efficacy of combinations of some medicinal plants used traditionally for treatment of malaria by the Meru community in Kenya.Gathirwa JW, Rukunga GM, Njagi EN, Omar SA, Mwitari PG, Guantai AN, Tolo FM. J Ethnopharmacol. 2008 Jan 17;115(2):223-31. Epub 2007 Sep 29.. : FA Okalebol , L Wiesner, AN Guantai, K Chibale, P Smith Abstract

The use of herbal drugs as combinations has existed for centuries in several cultural systems. However, the safety and efficacy of such combinations have not been validated. In this study, the toxicity, anti-plasmodial and antimalarial efficacy of several herbal drug combinations were investigated. Lannea schweinfurthii, Turraea robusta and Sclerocarya birrea, used by traditional health practitioners in Meru community, were tested for in vitro anti-plasmodial and in vivo anti-malarial activity singly against Plasmodium falciparum and Plasmodium berghei, respectively. Methanolic extract of Turraea robusta was the most active against Plasmodium falciparum D6 strain. Aqueous extracts of Lannea schweinfurthii had the highest anti-plamodial activity followed by Turraea robusta and Sclerocarya birrea. D6 was more sensitive to the plant extracts than W2 strain. Lannea schweinfurthii extracts had the highest anti-malarial activity in mice followed by Turraea robusta and Sclerocarya birrea with the methanol extracts being more active than aqueous ones. Combinations of aqueous extracts of the three plants and two others (Boscia salicifolia and Rhus natalensis) previously shown to exhibit anti-plasmodial and anti-malarial activity singly were tested in mice. Marked synergy and additive interactions were observed when combinations of the drugs were assayed in vitro. Different combinations of Turraea robusta and Lannea schweinfurthii exhibited good in vitro synergistic interactions. Combinations of Boscia salicifolia and Sclerocarya birrea; Rhus natalensis and Turraea robusta; Rhus natalensis and Boscia salicifolia; Turraea robusta and Sclerocarya birrea; and Lannea schweinfurthii and Boscia salicifolia exhibited high malaria parasite suppression (chemo-suppression >90%) in vivo when tested in mice. The findings are a preliminary demonstration of the usefulness of combining several plants in herbal drugs, as a normal practice of traditional health practitioners.

N, PROFGUANTAIA.  2008.  Establishment of a biobank and pharmacogenetics database of African populations.Matimba A, Oluka MN, Ebeshi BU, Sayi J, Bolaji OO, Guantai AN, Masimirembwa CM.Eur J Hum Genet. 2008 Jul;16(7):780-3. Epub 2008 Apr 2.. Eur J Hum Genet. 2008 Jul;16(7):780-3. Epub 2008 Apr 2.. : FA Okalebol , L Wiesner, AN Guantai, K Chibale, P Smith Abstract

The natural product curcumin has a wide range of useful biological effects. However its use in humans is limited due to its short half-life, rapid metabolism and poor oral bioavailability. It is metabolized by sequential reduction of carbon-carbon double two carbonyl groups. To overcome these limitations, a hydrazide derivative of curcumin was synthesized to improve its water solubility and reduce its rate of metabolism. The objective of study was, therefore, to develop a method for the analysis of hydrazinocureumin in murinc blood. This method will be eventually used to evaluate the pharmokinetic profile of hydrazinocurcumin in mice. Method: LC/MS/MS was selected as the analytic method because its high sensitivity allowed for sampling of small volumes of blood from mice. The optimal chromatographic and mass spectrometry conditions were determined by trial arid error. The column performance was monitored by measuring retention time, peak symmetry factor. A calibration curve was generated by using standard solutions with concentrations ranging from 0.78 - 10 rig/ml. The method was validated by determining the recovery, limit of detection, accuracy, linearity and intraday precision. The optimal method for extracting hydrazinocurcumin from biological fluids was determined by spiking human blood and plasma and extraction was done by solvent extraction from a spotted filter paper and liquid-liquid extraction. Instrumentation: The samples were assayed using an Agilent LC/MS/MS 3200Q Trap system (1100 series, USA) in the positive ionization mode. HPLC separation was done using an Agilent 1200 system (Agilent Technologies, Japan) interfaced with the MS/MS system. Ionization was done by electron spray ionization with a collision energy was 33eV. Chromatograms were integrated using Analyst version 1.4 software. Weighted linear regression was used to generate calibration curves from standard solutions. Results: The optimal conditions for HPLC separation was a mobile phase of 0.1% formic acid in acetonitrile: acetonitrile (1:1) with an isocratic flow rate of 0.3m1/minute and run time of 2 minutes. The analytical column was a 50 by 2.0 mm Pheromex C18 column with a particle size of 5 microns. The injection volume was 1 Out The hydrazinocurcumin formed molecular ion at M+H+ m/z 365.2 and two metastable ions at m/z 351 and m/z. 349.2. The transition monitored was m/z 365.2 to 349.2 at unit resolution and a dwelling time of 150 milliseconds. The retention time was 1.11 minutes. The optimal method of extraction was liquid-liquid extraction using 250 ul of ethyl acetate from 10 ul of whole blood in 50 ul of buffer at pH 10. The filter paper method of extraction was found to give erratic results. The calibration curve was linear over the concentration range of 10n/m1 to 0.5 ng/ml of hydrazinocurmin in whole human blood. Conclusion: The precision, accuracy, recovery and applicability were found to be adequate for pharmacokinetic studies in mice.

2007

Gathirwa, JW;, Rukunga GM;, Njagi ENM;, Omar SA;, Guantai AN;, Muthaura CN;, Mwitari PG;, Kimani CW;, Kirira PG;, Tolo FM;, Ndunda TN;, Ndiege IO.  2007.  In vitro anti-plasmodial and in vivo anti-malarial activity of some plants traditionally used for the treatment of malaria by the Meru community in Kenya. Abstract

Extracts of seven medicinal plant species used for treatment of malaria in traditional/cultural health systems of the Ameru people in Kenya were tested in vitro and in vivo against Plasmodium falciparum (D6 and W2 strains) and P. berghei, respectively. Of the plants tested, 28.57% were highly active (IC50 <10 μg/ml) and 42.86% moderately active (IC50 10–50 μg/ml), while 28.57% had weak activity of 50–125 μg/ml in vitro. The water and methanol extracts of Boscia salicifolia Oliv. and Artemisia afra Jacq. (ex-Willd.) were the most active against both the chloroquine (CQ)-sensitive (D6) and the CQ-resistant (W2) P. falciparum strains. Artemisia afra and Rhus natalensis Bernh. (ex-Krauss) exhibited the highest parasite clearance and chemo-suppression (>70%) in vivo (in mice). The plants with high in vitro anti-plasmodial (low IC50 values) and high anti-malarial activity (high chemo-suppression) in vivo are potential sources of novel anti-malarial drugs.

N, PROFGUANTAIA.  2007.  SE OF ELISA METHOD TO DETERMINE CHLORAMPHENICOL KINETICS IN RED MASAAI SHEEP AFTER INTRAMUSCULAR INJECTION. j. VET PHARMACO. THERAP. : O Wesongah*l, GA Murilla, AN Guantai, RE Mdachi I, WM Karanja and TE Maitho Abstract

hloramphenicol is a broad-spectrum antibiotic widely used in human and veterinary medicine due to its low cost and ready availability. However its use has been associated with serious adverse effects, (bone marrow suppression, hemolytic anaemia and aplastic anaemia) that may or may not be dose related. Consequently chloramphenicol is currently banned for use in food producing animals and restricted to non-food producing animals and management of life threatening infections in humans in absence of alternative therapy. Exposure to chloramphenicol can occur after regular consumption of animal foods from treated animals. Therefore the pharmacokinetic of chloramphenicol should be determined using a highly sensitive and specific assay method that can detect residue levels at the lowest concentration possible. Previous methods were limited due to low sensitivity (10 ng/m1-50Ong/mi). Therefore the aim of this study was to determine pharmacokinetics of chloramphenicol and potential residue levels in food producing animals using a published highly sensitive detection method; Chloramphenicol enzyme-linked immunosorbent assay, with a detection limit of 0.1 ng/ml. Methods: Eight male red Maasai sheep aged 9 to 12 months and weighing between 21kg to 25 kg, were weaned and allowed to acclimatize for three weeks. Pre-treatment blood samples (10m1) was collected from each animal and then 25mg/kg chloramphenicol sodium succinate administered by deep intramuscular injection. Post treatment blood samples were collected at 5, 10, 15 and 30minutes, I, 2, 4, 6 8, 12, 24 and 32 hour intervals then twice a day (week 1), once daily (week 2) thrice daily (week 3) twice daily (week 4). Phannacokinetic parameters were measured using chloramphenicol ELISA method. Data was analyzed by fitting four, parameter logistics regression curve of calibration standards and sample chloramphenicol concentration calculated from optical densities using ELISA data Eiaquik program (MC. Eisler, 1995). Samples were analyzed in duplicate. Results from these assays were compared with those from published data with respect to elimination half life, species variation, and minimum retention time. Results: Chlorarnphenicol elimination half life (36.4+3.66 h) obtained in the present study was significantly (P<0.05) longer than that of 5.75+1.25 h reported in similar species using colorimetric method. The method was able to detect the drug 7 days post administration. The area under the curve of 124,487.8 ng.h/m1 observed in sheep in the present study was significant higher than that of 31.220+3.25 rig.himl reported in literature in goats using similar treatment route and dose but different assay method. Conclusion: Chloramphenicol pharmacokinetic parameters are significantly influenced by animal species and analytical assay methods used in their determination and care must be taken when reporting the residue levels in food producing animals.

N, PROFGUANTAIA.  2007.  Antimalarial activity of some plants traditionally used in Meru district of Kenya.Muthaura CN, Rukunga GM, Chhabra SC, Omar SA, Guantai AN, Gathirwa JW, Tolo FM, Mwitari PG, Keter LK, Kirira PG, Kimani CW, Mungai GM, Njagi EN.Phytother Res. 2007 Sep;21(9). Phytother Res. 2007 Sep;21(9):860-7.. : FA Okalebol , L Wiesner, AN Guantai, K Chibale, P Smith Abstract

Ten plant extracts commonly used by the Meru community of Kenya were evaluated for the in vitro antiplasmodial, in vivo antimalarial, cytotoxicity and animal toxicity activities. The water and methanol extracts of Ludwigia erecta and the methanol extracts of Fuerstia africana and Schkuhria pinnata exhibited high antiplasmodial activity (IC(50) < 5 microg/mL) against chloroquine sensitive (D6) and resistant (W2) Plasmodium falciparum clones. The cytotoxicity of these highly active extracts on Vero E6 cells were in the range 161.5-4650.0 microg/mL with a selectivity index (SI) of 124.2-3530.7. In vivo studies of these extracts showed less activity with chemosuppression of parasitaemia in Plasmodium berghei infected mice of 49.64-65.28%. The methanol extract of Clerodendrum eriophyllum with a lower in vitro activity (IC(50) 9.51-10.56 microg/mL) exhibited the highest chemosuppression of 90.13%. The methanol and water extracts of Pittosporum viridiflorum were toxic to mice but at a lower dose prolonged survival of P. berghei infected mice (p < 0.05) with no overt signs of toxicity. However, the extracts were cytotoxic (SI, 0.96-2.51) on Vero E6 cells. These results suggest that there is potential to isolate active non-toxic antimalarial principles from these plants.

N, PROFGUANTAIA, N PROFGUANTAIA, N PROFGUANTAIA.  2007.  A competitive enzyme-linked immunosorbent assay for determination of chloramplienicol. j. VET PHARMACO. THERAP. : J. 0. WESONGAH* G. A. MUMMA* A. N. GUANTAI C. ELLIOT T FODEY1 & A. CANNA VAN Abstract

Chloramphenicol is a broad-spectrum antibioi ic shown to have specific activity against a wide variety of organisms that are causative agents of several disease conditions in domestic animals. Chloramphenicol has been banned for use in food-producing animals for its serious adverse toxic effects in humans. Due to the harmful effects of chloramphenicol residues livestock products should be free of any traces of these residues. Several analytical methods are available for chloramphenicol analysis hut sensitive methods are required in order to ensure that no traces of chloramphenicol residues are present in edible animal products. In order to prevent the illegal use of chloramphenicol, regulatory control of its residues in food of animal origin is essential. A competitive enzyme-linked immunosorbent assay for chloramphenicol has been locally developed and optimized for the detection of chloramphenicol in sheep serum. fn the assay, chloramphenicol in the test samples and that. in chloramphenicol-horseradish peroxidase conjugate compete for antibodies raised against the drug in camels and immobilized on a microtitre plate. Tetramethylbenzidine-hydrogen peroxide (Th413/11202) is used as chromogen-substrate system. The assay has a detection limit of 0.1 ng/ml, of serum with a high specificity for chloramphenicol. Cross-reactivity with florfenicol, thiamphenicol, penicillin, tetracyclines and sulfa-methazine was not observed. The assay was able to detect chloramphenicol concentrations in normal sheep serum for at least 1 week after intramuscular Injection with the drug at a dose of 25 mg/kg body weight (b.w.). The assay can be used as a screening tool for chloramphenicol use in animals. Paper received 27 July 2006; accepted for publication 29 September 2006 1.0. Wesongaii, Kenya Agricultural Research Institute-Trypanosmniasis Research Centre

N, PROFGUANTAIA.  2007.  Antimalarial activity of some plants traditionally used in treatment of malaria in Kwale district of Kenya.Muthaura CN, Rukunga GM, Chhabra SC, Omar SA, Guantai AN, Gathirwa JW, Tolo FM, Mwitari PG, Keter LK, Kirira PG, Kimani CW, Mungai GM, Njagi EN.J Et. J Ethnopharmacol. 2007 Jul 25;112(3):545-51. Epub 2007 May 5.. : FA Okalebol , L Wiesner, AN Guantai, K Chibale, P Smith Abstract

Methanolic and water extracts of five medicinal plant species used for treatment of malaria in traditional/cultural health systems of Kwale people in Kenya were tested for antimalarial activity against Plasmodium falciparum and Plasmodium berghei, respectively and for their cytotoxic effects. The most active extracts (IC(50)<10 microg/ml) screened against chloroquine (CQ) sensitive (D6) and resistant (W2) P. falciparum clones, were the water and methanol extracts of Maytenus undata (Thunb.) Blakelock (Celasteraceae), methanol extracts of Flueggea virosa (Willd.) Voigt (Euphorbiaceae), Maytenus putterlickioides (Loes.) Excell and Mendoca (Celastraceae), and Warburgia stuhlmannii Engl. (Canellaceae). These extracts showed various cytotoxic levels on Vero E6 cells with the water extract of M. undata exhibiting least cytotoxicity. At least one of the extracts of the plant species exhibited a high chemo suppression of parasitaemia >70% in a murine model of P. berghei infected mice. These results indicate that there is potential for isolation of a lead compound from the extracts of the five plants. W. stuhlmannii and M. putterlickioides have not been reported before for antiplasmodial activity.

N, PROFGUANTAIA.  2007.  A competitive enzyme-linked immunosorbent assay for determination of chloramphenicol.Wesongah JO, Murilla GA, Guantai AN, Elliot C, Fodey T, Cannavan A.J Vet Pharmacol Ther. 2007 Feb;30(1):68-73.. J Vet Pharmacol Ther. 2007 Feb;30(1):68-73.. : FA Okalebol , L Wiesner, AN Guantai, K Chibale, P Smith Abstract

Chloramphenicol is a broad-spectrum antibiotic shown to have specific activity against a wide variety of organisms that are causative agents of several disease conditions in domestic animals. Chloramphenicol has been banned for use in food-producing animals for its serious adverse toxic effects in humans. Due to the harmful effects of chloramphenicol residues livestock products should be free of any traces of these residues. Several analytical methods are available for chloramphenicol analysis but sensitive methods are required in order to ensure that no traces of chloramphenicol residues are present in edible animal products. In order to prevent the illegal use of chloramphenicol, regulatory control of its residues in food of animal origin is essential. A competitive enzyme-linked immunosorbent assay for chloramphenicol has been locally developed and optimized for the detection of chloramphenicol in sheep serum. In the assay, chloramphenicol in the test samples and that in chloramphenicol-horseradish peroxidase conjugate compete for antibodies raised against the drug in camels and immobilized on a microtitre plate. Tetramethylbenzidine-hydrogen peroxide (TMB/H(2)O(2)) is used as chromogen-substrate system. The assay has a detection limit of 0.1 ng/mL of serum with a high specificity for chloramphenicol. Cross-reactivity with florfenicol, thiamphenicol, penicillin, tetracyclines and sulfamethazine was not observed. The assay was able to detect chloramphenicol concentrations in normal sheep serum for at least 1 week after intramuscular injection with the drug at a dose of 25 mg/kg body weight (b.w.). The assay can be used as a screening tool for chloramphenicol use in animals.

2006

Kamau, FN, Kibwage IO, Muriuki G, Guantai, A N, Chepkwony H, Hoogmartens J, Roets E, Busson R.  2006.  Steroidal Indoxyls: Evaluation of Pk, values and anti-inflammatory activity. Abstract

Three steroidal indoxyls, 3-oxo-16,17-seco-16;.nor-l,4-androstadien-15-(7'-methoxy-2-indoxyliden)17-oic acid, 1-(2'-indoxyliden)-2-nor-l,2-secocholestan-3~ oic acid and 1-(5'- chloro-2-indoxyliden)-2-nor-l,2-secocholestan-3-oic acid were synthesized and screened for anti-inflammatory activity. Their pK. values were also determined using a solubility method. The first compound, 3-oxo-16,17- seco-16-nor-l ,4-androstadien-15-(7' -methoxy-2-indoxyliden) 17 -oic acid, had an EDso value of 15.3 mg/kg and a pK. of 7.09. The cholestane derivative, 1-(2'-indoxyliden)-2-nor-l,2-secocholestan-3-oic acid, and its chloro analogue 1-(5'-chloro-2-indoxyliden)-2-nor-l,2-secocholestan-3-oic acid had EDso values of 16.2 and 22.8 mg/kg, while their pK. values were 6.56 and 7.07, respectively, suggesting that these compounds are relatively weak acids.

2003

N, PROFGUANTAIA.  2003.  Kamau F.N., Kibwage I.O, Guantai A.N. Muriuki G., Munenge, R.Anti-inflammatory and Anti-diarrhoea activities of a steroidal indoxyl: E. C. African Journal of Pharmaceutical Sciences Vol. 6 (2) pp 26. African Journal of Pharmaceutical Sciences Vol. 6 (2) pp 26 . : O Wesongah*l, GA Murilla, AN Guantai, RE Mdachi I, WM Karanja and TE Maitho Abstract

hloramphenicol is a broad-spectrum antibiotic widely used in human and veterinary medicine due to its low cost and ready availability. However its use has been associated with serious adverse effects, (bone marrow suppression, hemolytic anaemia and aplastic anaemia) that may or may not be dose related. Consequently chloramphenicol is currently banned for use in food producing animals and restricted to non-food producing animals and management of life threatening infections in humans in absence of alternative therapy. Exposure to chloramphenicol can occur after regular consumption of animal foods from treated animals. Therefore the pharmacokinetic of chloramphenicol should be determined using a highly sensitive and specific assay method that can detect residue levels at the lowest concentration possible. Previous methods were limited due to low sensitivity (10 ng/m1-50Ong/mi). Therefore the aim of this study was to determine pharmacokinetics of chloramphenicol and potential residue levels in food producing animals using a published highly sensitive detection method; Chloramphenicol enzyme-linked immunosorbent assay, with a detection limit of 0.1 ng/ml. Methods: Eight male red Maasai sheep aged 9 to 12 months and weighing between 21kg to 25 kg, were weaned and allowed to acclimatize for three weeks. Pre-treatment blood samples (10m1) was collected from each animal and then 25mg/kg chloramphenicol sodium succinate administered by deep intramuscular injection. Post treatment blood samples were collected at 5, 10, 15 and 30minutes, I, 2, 4, 6 8, 12, 24 and 32 hour intervals then twice a day (week 1), once daily (week 2) thrice daily (week 3) twice daily (week 4). Phannacokinetic parameters were measured using chloramphenicol ELISA method. Data was analyzed by fitting four, parameter logistics regression curve of calibration standards and sample chloramphenicol concentration calculated from optical densities using ELISA data Eiaquik program (MC. Eisler, 1995). Samples were analyzed in duplicate. Results from these assays were compared with those from published data with respect to elimination half life, species variation, and minimum retention time. Results: Chlorarnphenicol elimination half life (36.4+3.66 h) obtained in the present study was significantly (P<0.05) longer than that of 5.75+1.25 h reported in similar species using colorimetric method. The method was able to detect the drug 7 days post administration. The area under the curve of 124,487.8 ng.h/m1 observed in sheep in the present study was significant higher than that of 31.220+3.25 rig.himl reported in literature in goats using similar treatment route and dose but different assay method. Conclusion: Chloramphenicol pharmacokinetic parameters are significantly influenced by animal species and analytical assay methods used in their determination and care must be taken when reporting the residue levels in food producing animals.

N, PROFGUANTAIA.  2003.  Anti-infiammatory and Anti-Diarrimeai Activities of a Steroidal indoxy. East and Central African Journal of Pharmaceutical Sciences 6. : F. N. KAMAU., 1.0. KIBWAGE, A. N. GUANTAI, G. MURIUKI R. MUNENGE Abstract

The anti-inflammatory and antidiarrhoeal activities of 3(1-Hydroxy-16. 17-seco-16- nor-5-androsten-15-(2-indoxyliden)-17-oic acid (I) are reported. After intraperitoneal administration, compound (I) gave an ED50 of 9.5 mg/kg using the carrageenan induced rat paw oedema anti-inflammatory assay method. Indomethacin had an ED50 of 5.8 mg/kg in this assay. Compound (I) and indomethacin caused comparable and dose-dependent varying degrees of delay in diarrhoea and also significantly reduced net colonic water flux into the colon of rats induced by castor oil. Key words: Steroidal Indoxyl, Anti-Inflammatory, Antidiarrhoeal.

2002

N, PROFGUANTAIA, N PROFGUANTAIA.  2002.  The Antimalarial and Antimicrobial Activity and Brine Shrimp Toxicity of Clematis Brachiata Extracts. East and Central African Journal of Pharmaceutical Sciences Vol. 5. : F.A. OKALEBO*, H.A. RABAHI, A.N. GUANTAII, C.K. MALTA', I.0. K1BWAGE, J.W. MWANGI AND W. MASENGO Abstract

The in vitro antimalarial activity of the root extract in partly supports the ethnobotanical use of the plant to manage malaria. Clematis brachiata Thunberg (Ranunculaceae) is used in Kenya for the management of headaches, malaria and other febrile illnesses, abdominal disorders, yaws and for skin disorders. Old stems and leaves are chewed for the management of toothaches and sore throats. Extracts of the plant were subjected to tests for antimalarial, antibacterial and antifungal activity. The toxicity of the extracts was assessed using the brine shrimp lethality bioassay. The root extract gave the highest in vitro antimalarial activity against the inulitidrug resistant strain, Plasmodium falciparum VI/S (IC50=39.24 jig/nil). The stem and leaf extracts had insignificant antiplasmodial activity. The leaf, stein and root extracts had no bacterial or fungal inhibitory effects even at very high concentrations of 10 mg/ml. The Lll50 values of the stem and leaf methanol extracts against the brine shrimp larvae was 365.60 and 66.5 jig/ml, respectively. Key Words: Clematis brachiata, Ranuneulaceae, antimalarial, antibacterial, antifungal, brine shrimp.

N, PROFGUANTAIA.  2002.  Kamau F,N. I.O.Kibwage, Muriuki G, Guantai A.N., Hoog martens J, Roets E, Govaerts, C; Chepkwony. H. and Busson R.Estrogenic and Anti-inflamatory activity of a steroidal. Idoxyl, The East and Central Journal of Pharmaceutical Sciences Vol. 5 (3) 44-48 Dec. The East and Central Journal of Pharmaceutical Sciences Vol. 5 (3) 44-48 Dec 2002. : F. N. KAMAU., 1.0. KIBWAGE, A. N. GUANTAI, G. MURIUKI R. MUNENGE Abstract

The anti-inflammatory and antidiarrhoeal activities of 3(1-Hydroxy-16. 17-seco-16- nor-5-androsten-15-(2-indoxyliden)-17-oic acid (I) are reported. After intraperitoneal administration, compound (I) gave an ED50 of 9.5 mg/kg using the carrageenan induced rat paw oedema anti-inflammatory assay method. Indomethacin had an ED50 of 5.8 mg/kg in this assay. Compound (I) and indomethacin caused comparable and dose-dependent varying degrees of delay in diarrhoea and also significantly reduced net colonic water flux into the colon of rats induced by castor oil. Key words: Steroidal Indoxyl, Anti-Inflammatory, Antidiarrhoeal.

2000

N, PROFGUANTAIA.  2000.  Guantai A.N and Addae-Mensah I.Chloroquine Drug Interactions Part 1I. Interactions with diuretics. East and Central African Journal of Pharmaceutical Sciences Vol (3. No.3, 31-35 (2000).. East and Central African Journal of Pharmaceutical Sciences Vol (3. No.3, 31-35 (2000).. : F.A. OKALEBO*, H.A. RABAHI, A.N. GUANTAII, C.K. MALTA', I.0. K1BWAGE, J.W. MWANGI AND W. MASENGO Abstract

The in vitro antimalarial activity of the root extract in partly supports the ethnobotanical use of the plant to manage malaria. Clematis brachiata Thunberg (Ranunculaceae) is used in Kenya for the management of headaches, malaria and other febrile illnesses, abdominal disorders, yaws and for skin disorders. Old stems and leaves are chewed for the management of toothaches and sore throats. Extracts of the plant were subjected to tests for antimalarial, antibacterial and antifungal activity. The toxicity of the extracts was assessed using the brine shrimp lethality bioassay. The root extract gave the highest in vitro antimalarial activity against the inulitidrug resistant strain, Plasmodium falciparum VI/S (IC50=39.24 jig/nil). The stem and leaf extracts had insignificant antiplasmodial activity. The leaf, stein and root extracts had no bacterial or fungal inhibitory effects even at very high concentrations of 10 mg/ml. The Lll50 values of the stem and leaf methanol extracts against the brine shrimp larvae was 365.60 and 66.5 jig/ml, respectively. Key Words: Clematis brachiata, Ranuneulaceae, antimalarial, antibacterial, antifungal, brine shrimp.

1998

N, PROFGUANTAIA.  1998.  Guantai A.N., Addae-Mensah I.,. Njoroge D.K.. Chloroquine Drug Interactions. Part I Interaction with drugs on the neuromuscular junction. The East and /central African Journal of Pharmaceutical Sciences Vol. 1 (3)-50-53 Dec. 1998. The East and /central African Journal of Pharmaceutical Sciences Vol. 1 (3)-50-53 Dec. 1998. : F.A. OKALEBO*, H.A. RABAHI, A.N. GUANTAII, C.K. MALTA', I.0. K1BWAGE, J.W. MWANGI AND W. MASENGO Abstract

The in vitro antimalarial activity of the root extract in partly supports the ethnobotanical use of the plant to manage malaria. Clematis brachiata Thunberg (Ranunculaceae) is used in Kenya for the management of headaches, malaria and other febrile illnesses, abdominal disorders, yaws and for skin disorders. Old stems and leaves are chewed for the management of toothaches and sore throats. Extracts of the plant were subjected to tests for antimalarial, antibacterial and antifungal activity. The toxicity of the extracts was assessed using the brine shrimp lethality bioassay. The root extract gave the highest in vitro antimalarial activity against the inulitidrug resistant strain, Plasmodium falciparum VI/S (IC50=39.24 jig/nil). The stem and leaf extracts had insignificant antiplasmodial activity. The leaf, stein and root extracts had no bacterial or fungal inhibitory effects even at very high concentrations of 10 mg/ml. The Lll50 values of the stem and leaf methanol extracts against the brine shrimp larvae was 365.60 and 66.5 jig/ml, respectively. Key Words: Clematis brachiata, Ranuneulaceae, antimalarial, antibacterial, antifungal, brine shrimp.

N, PROFGUANTAIA.  1998.  Chloroquine Drug Interactions Part I: Interaction with drugs acting at the neuromuscular junction. EAST AND CENTRAL AFRICAN JOURNAL OF PHARMACEUTICAL SCIENCES, VOL. I. : ANASTASIA N. GUANTAI , IVAN ADDAE-MENSAH, DAVID K. NJOROGE Abstract

Chloroquine is extensively used in the management of malaria in Kenya. It is widely available for self medication. Often it is used concurrently with other drugs. In the present paper, possible drug interactions with Chloroquine have been investigated. Isolated rat phrenic nerve diaphragm preparation was used to study the effect of Chloroquine alone and in combination with several drugs on neuromuscular impulse transmission. Chloroquine in the dose range 0.025 - 0.3 vg/m1 organ bath concentration induced a dose-dependent neuromuscular junction (NMJ) transmission blockade. The drug significantly potentiated the NMJ transmissionblockade induced by commonly used agents gallamine, succinylcholine and lignocaine. It antagonised the NMJ facilitatory action of physostigmine, calcium chloride and barium chloride. Chloraquine could. be interfering with ion conductance processes. It is suggested that Chloroquine should be used with caution in conditions characterised by muscle contractile disorders or during treatment with drugs that cause decreased skeletal muscle activity. Key Words: Chloroquine, interactions, neuromuscular junction.

N, PROFGUANTAIA.  1998.  Maitai C.K., Kibwage I.O., Guantai A.N., Ombega J.O and Ndemo F.A. A retrospective study of childhood poisoning in Kenya 1991-93 E.C.A.J. PSc. 1.7-10. 1998. E.C.A.J. PSc. 1.7-10. 1998. : F.A. OKALEBO*, H.A. RABAHI, A.N. GUANTAII, C.K. MALTA', I.0. K1BWAGE, J.W. MWANGI AND W. MASENGO Abstract

The in vitro antimalarial activity of the root extract in partly supports the ethnobotanical use of the plant to manage malaria. Clematis brachiata Thunberg (Ranunculaceae) is used in Kenya for the management of headaches, malaria and other febrile illnesses, abdominal disorders, yaws and for skin disorders. Old stems and leaves are chewed for the management of toothaches and sore throats. Extracts of the plant were subjected to tests for antimalarial, antibacterial and antifungal activity. The toxicity of the extracts was assessed using the brine shrimp lethality bioassay. The root extract gave the highest in vitro antimalarial activity against the inulitidrug resistant strain, Plasmodium falciparum VI/S (IC50=39.24 jig/nil). The stem and leaf extracts had insignificant antiplasmodial activity. The leaf, stein and root extracts had no bacterial or fungal inhibitory effects even at very high concentrations of 10 mg/ml. The Lll50 values of the stem and leaf methanol extracts against the brine shrimp larvae was 365.60 and 66.5 jig/ml, respectively. Key Words: Clematis brachiata, Ranuneulaceae, antimalarial, antibacterial, antifungal, brine shrimp.

1993

N, PROFGUANTAIA.  1993.  A Retrospective Study of Childhood Poisoning in Kenya. EAST AND CENTRAL AFRICAN JOURNAL OF PHARMACEUTICAL SCIENCES - VOL. 1. : CHARLES K. MAITAI*, ISAAC 0. KIBWAGE, ANASTASIA N. GUANTAI, JAMES N. OMBEGA AND FRANCIS A. NDEM0 Abstract

A literature survey revealed lack of adequate information on poisoning in Kenya, thus providing the impetus for the present work. In this, study, a 3 year retrospective survey of human poisoning in 19 Kenyan District, Provincial hospitals and Kenyatta National Hospital (KNH), representing approximately 40% of such public hospitals in the country, was carried out. Cases of poisoning were identified by diagnosis codes entered on hospital records at the time of discharge. A total of 1904 cases of poisoning were recorded and the information analyzed with particular focus on childhood poisoning. Distribution pattern with respect to poisoning agents, age and sex is presented. Children aged 0-5 years account for 29.78% while those aged 6-14 years account for 10.24% of cases of poisoning recorded. In the age group 0-5 years, Kerosine, drugs and organophosphates account for 41.09, 23.81 and 15.17% of poisoning cases respectively. It is concluded that any preventive measures targeted at children must focus on the 3 classes of poisons which together account for approximately 80% of all classes of poisoning in children.

1989

Muriuki, G, Addae-Mensah I, Guantai AN.  1989.  A Pharmacological Investigation of the Hypoglycemic Activity of Artemisia afra.
N, PROFGUANTAIA.  1989.  Comparative Examination of Two Zanthoxylum Benzophenanthridine Alkaloids for Cardiovascular Effects in Rabbits. EAST AND CENTRAL AFRICAN JOURNAL OF PHARMACEUTICAL SCIENCES - VOL. 1. : Ivan Addae-Mensah,t Rahab Munenge and Anastasia N. Guantai Abstract

Cardiovascular activities of nitidine chloride from Zanthoxylunt chalybeum have been compared with those of 9-methoxychelerythrine. Whereas nitidinc chloride was found to show significant hypotensive activity in rabbits, 9-methoxychelerythrine chloride showed no hypotensive activity. The effect of nitidine chloride on isolated rabbit heart was also compared with those of adrenaline and acetylcholine. 9-Methoxychelerythrine, which has hitherto been regarded as an artefact formed by recrystallization of chelerythrine base from methanol, has been shown in this work to be a true natural constituent of Zanthoxylum chalybeum. Keywords: 9-inethoxychelerythrine; nitidine chloride; cardiovascular properties; hypotensive effect; Zanthoxylum chalybeum.

1988

N, PROFGUANTAIA.  1988.  Mwangi J.W. Guantai A.N., Muriuki G., Kwande W.Constituents of the essential oil of ocimum fischeri guerke. Kenya J. Sci series (B) 9:119-121 1988. Kenya J. Sci series (B) 9:119-121 1988. : Ivan Addae-Mensah,t Rahab Munenge and Anastasia N. Guantai Abstract

Cardiovascular activities of nitidine chloride from Zanthoxylunt chalybeum have been compared with those of 9-methoxychelerythrine. Whereas nitidinc chloride was found to show significant hypotensive activity in rabbits, 9-methoxychelerythrine chloride showed no hypotensive activity. The effect of nitidine chloride on isolated rabbit heart was also compared with those of adrenaline and acetylcholine. 9-Methoxychelerythrine, which has hitherto been regarded as an artefact formed by recrystallization of chelerythrine base from methanol, has been shown in this work to be a true natural constituent of Zanthoxylum chalybeum. Keywords: 9-inethoxychelerythrine; nitidine chloride; cardiovascular properties; hypotensive effect; Zanthoxylum chalybeum.

W, PROFMWANGIJULIUS, N PROFGUANTAIA.  1988.  J.W. Mwangi, G. Muriuki, A.N. Guantai and W. Lwande (1988). Volatile constituents of Ocimum fischeri Guerke. Kenya J. Sci. B.9: 119-121. Kenya J. Sci. B.9: 119-121. : Ivan Addae-Mensah,t Rahab Munenge and Anastasia N. Guantai Abstract

Cardiovascular activities of nitidine chloride from Zanthoxylunt chalybeum have been compared with those of 9-methoxychelerythrine. Whereas nitidinc chloride was found to show significant hypotensive activity in rabbits, 9-methoxychelerythrine chloride showed no hypotensive activity. The effect of nitidine chloride on isolated rabbit heart was also compared with those of adrenaline and acetylcholine. 9-Methoxychelerythrine, which has hitherto been regarded as an artefact formed by recrystallization of chelerythrine base from methanol, has been shown in this work to be a true natural constituent of Zanthoxylum chalybeum. Keywords: 9-inethoxychelerythrine; nitidine chloride; cardiovascular properties; hypotensive effect; Zanthoxylum chalybeum.

1987

N, PROFGUANTAIA.  1987.  EFFECTS OF THE ACTIVE CONSTITUENTS OF CATHA EDULIS ON THE NEUROMUSCULAR JUNCTION. Pergarnon Journals Ltd. : A. N. GUANTAI, J. W. MWANG1, G1CHURU MURIUKI and K. A. M. KURIA

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