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W PROFMWANGIJULIUS, N PROFGUANTAIA. "C.K. Maitai, A.N. Guantai and J.W. Mwangi (1981). Self-medication in management of minor health problem in Kenya. E.A. Medical J. 58: 593-600.". In: E.A. Medical J. 58: 593-600. A.N. GUANTAI and C.K. MAITA; 1981. Abstract
he distribution of cathinone and d-norpseudoephedrine in Catha edit/is plants from 2 different geographical localities has been investigated. There was no difference in the chemical constituents of Catha material from 2 locali-ties. D-norpseudoephedrine was present in all parts of the plant examined except the root but cathinone was only detected in the young shoots and bran-chlets. It is concluded that the psychostinaulant effect following chewing of young Catha shoots is due to both cathinone and d-norpseudoephedrine with the cathinone being more important since it is 7-10 times more potent than d-norpseudoephedrine.
Oluka MN, Matimba A, Okalebo FA, Osanjo GO, Guantai AN, Masimirembwa CM. "Characterization of inter-ethnic genetic variability of CYP2D6, CYP2C19, CYP2B6, NAT2 and GSTs in the Bantu and Nilotic populations of Kenya and implications for the chemotherapy of infectious diseases." African Journal of Pharmacology and Therapeutics. 2014;3(2):38-46. Abstract2014_-_characterisation_of_interethnic_genetic_variability_of_cyp2d6cyp2c19--.pdf

Background: Drug metabolism genes are variable in populations. African populations are highly genetically
differentiated. Analysis of drug metabolism genes offers opportunities to enhance drug efficacy and reduce toxicity.

Objectives: We characterized SNPs of CYP2D6, CYP2C19, CYP2B6, NAT2 and GST genes in Kenyans.

Methodology: Genotyping of CYP2C19 (*2, *3); CYP2B6 (*6); CYP2D6 (*2,*4, *17, *29); NAT2 (*5, *6, *7, *14); GSTM1 and GSTT1 by PCR-RFLP.

Results: CYP2D6*4 was higher in Eastern Nilotes (9%) compared to Western Nilotes (2.5%) and Bantus (1.7%) (P = 0.002). CYP2D6*17 was higher in Bantus (34%) compared to Nilotes (18 – 23%) (P = 0.003). GSTM1del was higher in Western Nilotes and Bantus (29% -31%) compared to Eastern Nilotes (16%) (P = 0.009). GSTT1del was higher in Eastern Nilotes (41%) compared to Bantus and Western Nilotes (22 - 26%) (P = 0.005). CYP2C19*3 was undetected in Bantus but was >1.0% in Nilotes ((P <0.01). CYP2C19*2 (10 – 18%), CYP2B6*6 (35 – 37%), NAT2*5 (30 – 42%), NAT2*6 (20 – 27%), NAT2*7 (2 – 6%), NAT2*14 (8-14%) were similar in Kenyans. Kenyan frequencies were comparable to other Africans but different from caucasians and Asians.

Discussion: Variability was evident for CYP2D6*4, CYP2D6*17, GSTM1del and GSTT1del. Findings provide a
framework for Pharmacogenomic optimization of therapeutic outcomes.

Key Words: Pharmacogenomics, Drug metabolism, inter-ethnic variability, Kenyans

N PROFGUANTAIA. "Chloroquine Drug Interactions Part I: Interaction with drugs acting at the neuromuscular junction.". In: EAST AND CENTRAL AFRICAN JOURNAL OF PHARMACEUTICAL SCIENCES, VOL. I. ANASTASIA N. GUANTAI , IVAN ADDAE-MENSAH, DAVID K. NJOROGE; 1998. 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. "Comparative Examination of Two Zanthoxylum Benzophenanthridine Alkaloids for Cardiovascular Effects in Rabbits.". In: EAST AND CENTRAL AFRICAN JOURNAL OF PHARMACEUTICAL SCIENCES - VOL. 1. Ivan Addae-Mensah,t Rahab Munenge and Anastasia N. Guantai; 1989. 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.

N PROFGUANTAIA. "Comparative tolerability and efficacy of stavudine 30 mg versus stavudine 40 mg in patients on combination antiretroviral therapy in Kenya.". In: ournal of AIDS and HIV Research Vol. 2(2) pp. 024-031. Monicah Wanjiru Karara, Faith Apolot Okalebo, Margaret Ng; 2010. 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.

N PROFGUANTAIA. "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.". In: J Vet Pharmacol Ther. 2007 Feb;30(1):68-73. FA Okalebol , L Wiesner, AN Guantai, K Chibale, P Smith; 2007. 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.

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

Oluka MN, Okalebo FA, Guantai AN, McClelland S, Graham SM. "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. 2015;12(10):DOI 10.1186/s12981-015-0052-0. Abstract2015_-_cytochrome_p450_genetic_variants_nevirapine.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

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