Evaluation of Zidovudine, Lamivudine and Nevirapine Plasma Concentrations and Factors influencing their Plasma Drug Exposure in Children Aged 2–14 Years Living with HIV at the Lagos University Teaching Hospital
(1) Department of Pharmacology, Therapeutics and Toxicology, Faculty of Basic Medical Sciences, College of Medicine, University of Lagos, Idi-Araba, P.M.B. 12003, Lagos, Nigeria
(2) Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Lagos, Idi-Araba, P.M.B. 12003, Lagos, Nigeria
(3) Department of Pharmacology, Therapeutics and Toxicology, Faculty of Basic Medical Sciences, College of Medicine, University of Lagos, Idi-Araba, P.M.B. 12003, Lagos, Nigeria
(4) Department of Haematology and Blood Transfusion, Faculty of Clinical Sciences, College of Medicine, University of Lagos, Idi-Araba, P.M.B. 12003, Lagos, Nigeria
(5) Department of Pharmacology, Therapeutics and Toxicology, Faculty of Basic Medical Sciences, College of Medicine, University of Lagos, Idi-Araba, P.M.B. 12003, Lagos, Nigeria
Corresponding Author
Abstract
Background: Plasma concentrations of antiretroviral drugs have become important determinants of treatment success, treatment failure and toxicity. There is a paucity of antiretroviral plasma concentration data in our local paediatric human immunodeficiency virus (HIV) literature in Nigeria.
Objective: To evaluate plasma concentrations of zidovudine, lamivudine, and nevirapine after 2 years of combination therapyand to determine factors that influence plasma drug exposure in children aged 2–14 years living with HIV.
Subjects and Methods: This was a cross-sectional prospective study in which plasma concentrations of zidovudine, lamivudine and nevirapine were simultaneously determined using a simple, rapid and sensitive high performance liquid chromatographic method with UV detection. Plasma concentrations obtained were compared to published data (Cmin and Cmax ) and regulatory reference data (C max only).
Results: The median plasma concentrations were 0.062, 1.435 and 4.450 μg/mL for zidovudine, lamivudine and nevirapine respectively. Supratherapeutic plasma zidovudine, lamivudine and nevirapine levels occurred in 33%, 22% and 26% of patients respectively. Supratherapeutic levels were however not significantly associated with adverse events (p>0.05).At 2 years,age (p=0.018) was significantly associated with zidovudine concentrations, with older children having higher levels. There was a perfect agreement between adherence and plasma concentrations of nevirapine (p=0.020).
Conclusion: Plasma concentrations were similar to levels previously reported in children with therapeutic, supratherapeutic and nevirapine supratherapeutic levels. There were no observed significant associations between plasma drug concentrations and toxicity. The clinical relevance of observed significant higher levels of plasma zidovudine with increasing age, and supratherapeutic plasma exposures of zidovudine, lamivudine and nevirapine needs further investigations.
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