Evaluation of the effects of atazanavir-ritonavir on the pharmacokinetics of lumefantrine in patients living with HIV in Lagos University Teaching Hospital, South Western Nigeria
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Date
2021-03-23
Authors
Usman, S.O.
Oreagba, I.A
Kadiri, M.R.
Adewunmi, O.O.
Akinyede, A.
Agbaje, E.O.
Busari, A.A.
Hassan, O.O.
Akinleye, M.O.
Akanmu, A.S.
Journal Title
Journal ISSN
Volume Title
Publisher
Springer
Abstract
Purpose
Atazanavir-ritonavir (ATVr)-based antiretroviral therapy and artemether-lumefantrine (AL) are commonly used drugs for the treatment of human immune deficiency virus (HIV) infection and malaria respectively. However, interaction of both drugs, with Cytochrome P 3A4 (CYP 3A4) isoenzyme, may spawn clinically significant pharmacokinetic interactions. This study evaluated the effects of atazanavir-ritonavir on the pharmacokinetics of lumefantrine.
Method
In a case-control study, twenty participants having Plasmodium falciparum malaria were recruited and divided into two groups (ATVr-arm, n=10; and control-arm, n= 10). All the participants were administered six oral doses of AL 80-480 mg (Coartem). Thereafter, their blood samples were collected at different time intervals over seven days. The concentration of lumefantrine in each sample was quantified with high-performance liquid chromatography (HPLC) and used to determine its pharmacokinetic parameters which were compared between the test and control groups.
Results
ATVr increased the mean day 7 concentration of lumefantrine (ATVr 3847.09 ± 893.35 ng/mL, control 1374.53 ± 265.55 ng/mL, p = 0.016) and the area under its plasma concentration-time curve (ATVr 670529.57 ± 157172.93 ng.h/mL, control 447976.28 ± 80886.99 ng.h/mL, p = 0.224) by 179.88 % and 49.68 %, respectively, but decreased its mean maximum plasma drug concentration (Cmax) (ATVr 13725.70 ± 2658.44 ng/mL, control 15380.48 ± 2332.62 ng/mL, p = 0.645) by 10.76 %.
Conclusion
ATVr increased drug exposure and day 7 plasma concentration of lumefantrine. AL is therefore considered effective for the treatment of malaria in patients taking ATVr-based regimen. However, the safety associated with the interaction requires further elucidation.
Description
Keywords
Lumefantrine , Atazanavir-ritonavir , Pharmacokinetic , Interaction , HIV
Citation
Usman, S. O., Oreagba, I. A., Kadri, M. R., Adewumi, O. O., Akinyede, A., Agbaje, E. O., ... & Akanmu, A. S. (2021). Evaluation of the effects of atazanavir-ritonavir on the pharmacokinetics of lumefantrine in patients living with HIV in Lagos University Teaching Hospital, South-Western Nigeria. European Journal of Clinical Pharmacology, 1-8.