HIV/AIDS Patients Display Lower Relative Bioavailability of Efavirenz than Healthy Subjects | SpringerLink Abstract Background: Pharmacokinetic studies of antiretroviral drugs are often conducted in adult healthy subjects, and the results are extrapolated to HIV/AIDS patients. HIV/AIDS, however, is known to cause morphological and physiological changes that may alter the pharmacokinetics of antiretroviral drugs. We examined the effect of HIV/AIDS on the pharmacokinetics of efavirenz in Ugandans. Methods: After a first oral dose of efavirenz 600 mg in treatment-naïve HIV-infected patients, blood samples were collected at nine time points up to 24 hours. The plasma-concentration time data from these patients were merged with previously reported data from adult healthy subjects. Population pharmacokinetic models were fitted to the data, using NONMEM VI software. Covariate analyses were performed to estimate the effects of HIV/AIDS disease, demographic characteristics (sex, bodyweight, age), biochemical variables (serum creatinine, urea, alanine aminotransferase) and pharmacogenetic variation in cytochrome P450 (CYP) 2B6, CYP3A5 and adenosine triphosphate-binding cassette, sub-family B, member 1 (ABCB1) on the population pharmacokinetic parameters. Results: Efavirenz plasma concentration-time data obtained from 29 HIV-1-infected, treatment-naïve patients were merged with previously reported data from 32 adult healthy subjects. The model identified sex and HIV/AIDS disease as statistically significant categorical predictors of efavirenz pharmacokinetics. Females were predicted to have a 2-fold higher volume of distribution of the peripheral compartment after oral administration (V2/F) than males (95% CI 1.53,2.63), while HIV/AIDS patients were found to have 30% lower relative bioavailability (95% CI 18.7, 40.7) than healthy subjects. 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SWE 2004-098, HIV-2006-031 and SWE 2007-270; the Makerere University-Karolinska Institutet research collaboration; and European and Developing Countries Clinical Trials Partnership (EDCTP) grant no. CT.2005.32030.001.Daniel Röshammar is an employee of AstraZeneca. However, this work was not funded or supported by any pharmaceutical company. All authors have no conflicts of interest that are directly relevant to the content of this study.Author informationAffiliationsDivision of Clinical Pharmacology, Department of Laboratory of Medicine, Karolinska University Hospital Huddinge, Karolinska Institutet, C-168, SE-141 86, Stockholm, SwedenJackson K. Mukonzo, Sarah Nanzigu, Lars L. Gustafsson    Eleni AklilluDepartment of Pharmacology and Therapeutics, Faculty of Medicine, Makerere University, Kampala, UgandaJackson K. Mukonzo, Sarah Nanzigu, Paul Waako   Jasper Ogwal-OkengUnit for Pharmacokinetics and Drug Metabolism, Department of Pharmacology, Sahlgrenska Academy at University of Gothenburg, Gothenburg, SwedenDinko Rekić   Michael AshtonAstraZeneca R D, Mölndal, SwedenDaniel RöshammarAuthorsJackson K. MukonzoView author publicationsYou can also search for this author in PubMed Google ScholarSarah NanziguView author publicationsYou can also search for this author in PubMed Google ScholarDinko RekićView author publicationsYou can also search for this author in PubMed Google ScholarPaul WaakoView author publicationsYou can also search for this author in PubMed Google ScholarDaniel RöshammarView author publicationsYou can also search for this author in PubMed Google ScholarMichael AshtonView author publicationsYou can also search for this author in PubMed Google ScholarJasper Ogwal-OkengView author publicationsYou can also search for this author in PubMed Google ScholarLars L. GustafssonView author publicationsYou can also search for this author in PubMed Google Scholar Eleni AklilluView author publicationsYou can also search for this author in PubMed Google ScholarAdditional informationAn erratum to this article is available at http://dx.doi.org/10.2165/11595800-000000000-00000.Rights and permissionsReprints and PermissionsAbout this articleCite this articleMukonzo, J.K., Nanzigu, S., Rekić, D. et al. HIV/AIDS Patients Display Lower Relative Bioavailability of Efavirenz than Healthy Subjects. Clin Pharmacokinet 50, 531–540 (2011). https://doi.org/10.2165/11592660-000000000-00000Download citationPublished: 13 September 2012Issue Date: August 2011DOI: https://doi.org/10.2165/11592660-000000000-00000KeywordsEfavirenzAtazanavirObjective Function ValueVisual Predictive CheckAdult Healthy Subject

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