Publications

Found 18 results

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1996
OLUKA DRODECKMARGRET. "Oluka MO, Mitema ES, Kibwage IO, Kwasa TO, Kokwaro GO. (1996) A comparative bioavailability of four Carbamazepine tablet formulations available in the Kenyan market.". In: East Afr Med J. 1996 May;73(5):323-6. Journal of Mathematics and Mathematical Sciences(PMMS); 1996. Abstract
Department of Pharmacology and Toxicology, University of Nairobi, Kenya. The relative bioavailabilities of three carbamazepine tablet formulations available in the Kenyan market (Temporal(R), Taver(R) and Carbamazepine Lincoln) compared with the innovator formulation (Tegretol(R)) were evaluated in seven healthy African volunteers (5 males, two females; aged 22-36 years), according to a randomised fourway crossover study design, following oral administration of single 200 mg doses with a three week washout period. In vitro dissolution profiles of the tablets were also evaluated. Relative bioavailabilities ((F)rel) of Temporal(R), Taver(R) and Carbamazepine Linocoln were 101.2%, 82.2% and 71.6% respectively, compared with Tegretol(R). Percent drug content dissolved in vitro after I hour were 91.3%, 75.9% and 39.3% for Temporal(R), Taver(R) and Carbamazepine Lincoln, respectively. It was concluded that Temporal(R) was bioequivalent to Tegretol(R) while Taver(R) and Carbamazepin Lincoln were bioinequivalent to Tegretol(R). Administration of Taver(R) or Carbamazepine Lincoln might lead to poor control of epileptic seizures.
2008
Matimba A, Oluka MN, Ebeshi BU, others. "Establishment of a biobank and pharmacogenetics database of African populations." European Journal of Human Genetics.. 2008;16:780-783.
2010
Karara MW, Okalebo FA, Oluka MO, Ombega J, Guantai AN, Osanjo GO. "Comparative tolerability and efficacy of stavudine 30 mg versus stavudine 40 mg in patients on combination antiretroviral therapy in Kenya." Journal of AIDS and HIV Research. 2010;2(2):024-031.
2011
Ong’ayo MN, Osanjo GO, Oluka MO. "Adherence to Anti-Tuberculosis Treatment among Paediatric Patients at Kenyatta National Hospital.". In: 1st International Scientific Conference, College Of Health Sciences, University Of Nairobi.; 2011.
Osanjo G, Aluvaala E, Wadegu M, Bulimo W, Guantai AN, Okalebo FA, Oluka M, Mulaa F. "Carbohydrate active enzymes (Cazymes) as drug targets and tools for synthesis of medicinal compounds.". In: 1st International Scientific Conference, College Of Health Sciences, University Of Nairobi.; 2011.
2012
2013
Okalebo FA, Ngaruiya MN, Changwony P, Oluka MN, Karume DW, Maloba KN. "The antinociceptive effects of Hydrazinocurcumin." Afr. J. Pharmacol. Ther.. 2013;2(2):66-69.
Wata DE, Osanjo GO, Oluka MN, Guantai AN. "Predictors of Breast Cancer Treatment Outcomes in Kenyan Women." Afr. J. Pharmacol. Ther.. 2013;2(4):109-115.
2014
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." Afr. J. Pharmacol. Ther.. 2014;3(2):38-46. Abstractoluka_et_al_2014.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

Ong'ayo MN, Osanjo GO, Oluka MN. "Determinants of Adherence to Anti-Tuberculosis Treatment among Pediatric Patients in Urban Kenya." Afr. J. Pharmacol. Ther.. 2014;3(1):1-7.
Ebeshi BU, Bolaji OO, Oluka MN, Edebi VN, Soyinka JO, Guantai AN. "Simple Reversed-Phase High Performance Liquid Chromatographic Estimation of the Antiretroviral Agent Efavirenz from Human Plasma." Br. J. Pharmaceut. Res. . 2014;4(1):145-157.
2015
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. Abstractoluka_et_al_2015.pdf

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

Kaburi AN, Oluka MO, Kosgei RJ, Mulwa NC, Maitai CK. "Herbal remedies and other risk factors for preterm birth in rural Kenya." Afr. J. Pharmacol. Ther.. 2015;4(4):135-142. Abstractkaburi_et_al_2015.pdf

Background: Premature infants contribute substantially to infant morbidity and mortality especially in low resource settings. Information on herbal remedy use, previous preterm birth and low social-economic status and their association with incidence of preterm birth in Kenya is scanty.
Objectives: To determine the use of herbal remedy use in pregnancy, previous preterm birth and low socio-economic status as risk factors for Preterm Birth in Kitui County among the immediate post-partum mothers.
Methods: Unmatched case control study with a 1:4 ratio of cases to controls. The study was done in Kitui and Mwingi District Hospitals. A total of 107 mothers with preterm birth (cases) and 453 mothers with term births (controls) were eligible and administered structured interviews.
Results: Of the sample, 98% of cases resided in rural areas compared to 90% of controls. The cases had a higher parity and were more likely to belong to the lowest three and four levels of socio-economic status. On multivariate logistic regression analysis, predictors of preterm birth were: preeclampsia (OR=9.06 [2.60-31.63], p=0.001), previous preterm, (OR=9.31 [2.82-30.68], p<0.001), low socioeconomic status (OR=1.51 [1.05-2.16], p=0.03), herbal use in first trimester for 2-5 days (OR=11.10 [4.34-28.41], p<0.001), herbal use in first trimester for 6-10 days (OR=44.87,[4.99-403.87] p=0.001), and herbal use in second trimester for 6-10 days (OR=16.43 [4.53-59.57], p<0.001). Use of prescribed folic acid in second trimester for more than 31 days was associated with lower risk of preterm birth (OR=0.20 [0.12-0.34], p<0.001).
Conclusion: Herbal use in pregnancy regardless of gestation, previous preterm birth and low socio-economic status and are risk factors for preterm birth in Kitui County Kenya. Interventions targeted to reduction of these risk factors will be an important additional prong in the reduction of preterm birth.
Key words: Preterm birth, herbal remedy, risk factors

Ambetsa MO, Makori JO, Osanjo GO, Oluka MN, Maitai CK, Guantai AN, McClelland S, Okalebo FA. "Incidence and Risk Factors of Renal Dysfunction in Patients on Nevirapine-Based Regimens at a Referral Hospital in Kenya." Afr. J. Pharmacol. Ther.. 2015;4(2):48-58. Abstractambetsa_et_al_2015.pdf

Introduction: Nevirapine-based regimens are the most commonly used ART in Kenya. There is little literature on the renal toxicity of NNRTIS in Kenyan settings. Some studies in Asia have demonstrated an association of NNRTIs and renal toxicity. Given that NNRTIs may cause renal toxicity, clinical studies on their contribution to the same are required.
Objectives: To evaluate the incidence and risk factors for renal dysfunction in HIV adult patients on Nevirapine based regimens.
Methodology: The design was a descriptive (right censored arm) hospital based retrospective cohort study carried out at a national referral hospital. Ethical approval was obtained. The study population was patients on Nevirapine based regimens seen between May and August, 2014. Convenient sampling was used to recruit 241 patients. Estimated glomerular filtration rate (eGFR) was calculated using the Modification of Diet in Renal Disease (MDRD) formula. Patients with eGFR < 50ml/min/1.73m2 were considered to have renal dysfunction. Data obtained by the patient interviews and abstraction of patient files and was analyzed using STATA software. Ordered Logistic regression was used to identify covariates that determine the severity of renal dysfunction.
Results: The incidence of renal dysfunction was 4.3% (95% C.I, 1.68-6.94).Five (2.1%) patients had a low eGFR at baseline, while ten (8.3%) patients had elevated serum creatinine (above 120μg/l). None of the patients developed severe renal dysfunction. Seventy (32%) and ten (4.6%) had mild and moderate renal dysfunction respectively. The females had a higher risk of developing renal dysfunction (adjusted O.R 0.48 (95% C.I 0.24-1.04; p=0.04). Alcohol consumption was a significant predictor of renal dysfunction (adjusted O.R 1.84 (95% C.I 1.01-3.29; p=0.04). All fifteen patients with a BMI of over 18.5 had elevated eGFR of below 50ml/min/1.73m2. Patients who had been initiated on stavudine based regimens had the highest incidence of renal dysfunction.
Conclusion: Routine eGFR calculations should be done at each clinical visit. Early detection of risk factors and systematic screening should be advocated for improved patient care.
Key Words: Body Mass Index, Renal dysfunction, Stavudine, Nevirapine

Massele A, Burger J, Katende-Kyenda NL, Kalemeera F, Kenaope T, Kibuule D, Mbachu O, Mubita M, Oluka M, Olusanya A, Paramadhas BAD, van Zyl P, Godman B. "Outcome of the first Medicines Utilization Research in Africa group meeting to promote sustainable and rational medicine use in Africa." Expert Rev. Pharmacoecon. Outcomes Res.. 2015;15(6):885-888. Abstractoluka_massele_et_al_2015.pdf

The first Medicines Utilization Research in Africa group workshop and symposium brought researchers together from across Africa to improve their knowledge on drug utilization methodologies as well as exchange ideas. As a result, progress was made on drug utilization research and formulating future strategies to enhance the rational use of medicines in Africa. Anti-infectives were the principal theme for the 1-day symposium following the workshops. This included presentations on the inappropriate use of antibiotics as well as ways to address this. Concerns with adverse drug reactions and adherence to anti-retroviral medicines were also discussed, with poor adherence remaining a challenge. There were also concerns with the underutilization of generics. These discussions resulted in a number of agreed activities before the next conference in 2016

Makori J, Ambetsa M, Sinei KA, Osanjo GO, Guantai AN, McClelland S, Oluka MN, Okalebo FA. "Patterns and Risk Factors for Alanine Aminotransferase Elevation among HIV Patients on Nevirapine Regimens." Afr. J. Pharmacol. Ther.. 2015;4(2):59-66. Abstractmakori_et_al_2015.pdf

Background: Elevated levels of serum transaminases are often detected in HIV patients. This has often been attributed to hepatic effects of antiretroviral drugs.
Objective: To determine the pattern and risk factors for alanine aminotransferase elevation in HIV patients positive on nevirapine based regimens.
Methodology: We conducted a retrospective cohort study of HIV infected patients on nevirapine containing regimens who attended the Kenyatta National Hospital comprehensive care clinic between May and August 2014. We sampled participants by convenient sampling method. Generalized linear regression was performed to establish patterns and predictors for hepatotoxicity (grade 1-4) which were the primary outcomes of interest. Predictor variables that were included in the analysis include; demographic information, baseline ALT and CD4 levels, ART regimens, comorbidities and treatment duration.
Results: Risk factors for ALT elevation differed by gender. Predictor variables that were significantly associated with ALT elevation in both sexes included; elevated baseline ALT level [β=10.14 (95%CI 7.34- 12.96); P<0.001], [β=13.52 (95%CI 9.36 –17.68); P < 0.001] and renal disease [β=5.44 (95%CI 2.62 – 8.25); P <0.001], [β=11.52 (95%CI 3.46 – 19.60); P = 0.005] in females and males respectively. Ethnicity had a protective effect in both sexes; [β-6.61(95%CI- 9.28, -3.93); P< 0.001] in males and [β-1.20 (95% CI-2.39, -0.01); P= 0.048] in females. Among the different ethnic groups, Nilotes and Cushites had lower ALT levels compared to Bantus. Other factors that were significant included; smoking (P=0.001), concurrent illnesses (P=0.045), previous adverse drug reactions (P=0.040) in females and a longer duration of anti-retroviral therapy [β 1.81(95%CI 0.89 – 2.73); P < 0.001] in males. Poor adherence had a protective effect [β -1.62(95%CI -3.20, -0.04); P=0.045] among females, whereas initiation on AZT+3TC+NVP had a significant protective effect [β-7.80 (95%CI -13.96, -1.63); P=0.013] in males.
Conclusion: Creatinine and transaminase testing should be done routinely to deal with delayed hepatotoxicity in patients with abnormal ALT baseline levels.
Key words: Alanine aminotransferase, hepatotoxicity, nevirapine.

2016
Jomo SM, Amugune B, Sinei KA, Oluka M. "Assessing the Prevalence and Severity of Potential Drug-drug Interactions among Mentally Ill Inpatients." Indian Research Journal of Pharmacy and Science. 2016;8:331-343. Abstractjomo_et_al_2016.pdf

Mental health refers to a wider range of activities directly or indirectly related to the mental well-being. Mentally ill patients in Kenya are increasingly becoming prone to a high risk of polypharmacy, complex therapeutic regimen and frequent modification of therapy. The objective of this study was to assess the prevalence and severity of potential drug-drug interactions among mentally ill patients admitted at Mathari Mental Hospital in Nairobi County, Kenya. The study was designed in a retrospective descriptive cross-sectional study of medical records data of patients who had undergone mental treatment and were admitted at Mathari Mental Hospital between July and December 2013. This study focused on a population comprising of all mentally ill patients who were admitted and put on medication during the study period of either gender and ageing between 13 to 75 years. One hundred and seventy five patient files were sampled, married and unemployed patients had a statistically significant (p<0.05) association with a prevalence and severity of potentially serious drug interactions. Participants with bipolar mood disorder had a statistically significant association with potentially serious drug interactions [OR 4.39 CI (1.09, 17.46) p = 0.04].
There was a statistically significant association of potentially serious drug interactions with fluphenazine [OR 10.38 CI (4.66, 23.10) p<0.01) haloperidol [OR 4.39 CI (2.29, 8.41) p<0.01] and amitriptyline [OR 3.39 CI (1.36, 8.41) p=0.01]. Married, unemployed and patients on fluphenazine, haloperidol, amitriptyline and chlorpromazine were at a higher risk of having potentially serious drug-drug interactions. These drugs exhibited both pharmacodynamic and pharmacokinetic drug interaction mechanisms. We recommend continuous electrocardiogram for patients on specific antipsychotics like haloperidol.

KEY WORDS : Mental Health, Drug Interaction, Prescriptions

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