Trial reportClinical pharmacokinetics2011
HIV/AIDS patients display lower relative bioavailability of efavirenz than healthy subjects.
Trial report in Clinical pharmacokinetics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 12 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
12 citing papers in PubMed, 33 citations in OpenAlex.
- Early or deferred initiation of efavirenz during rifampicin-based TB therapy has no significant effect on CYP3A induction in TB-HIV infected patients.British journal of pharmacology · 2021Trial
- Findings from a pilot study of buprenorphine population pharmacokinetics: A potential effect of HIV on buprenorphine bioavailability.Drug and alcohol dependence · 2022Article
- 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 · 2021Article
- Strategies for Implementation Research to Investigate the Negative Pharmacokinetic Interaction Between Efavirenz and Dolutegravir.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2021Article
- Prevalence of ABCC3-1767G/A polymorphism among patients with antiretroviral-associated hepatotoxicity.Molecular genetics & genomic medicine · 2020Article
- Prediction of plasma efavirenz concentrations among HIV-positive patients taking efavirenz-containing combination antiretroviral therapy.Scientific reports · 2017Article
- Population Pharmacokinetic Model Linking Plasma and Peripheral Blood Mononuclear Cell Concentrations of Efavirenz and Its Metabolite, 8-Hydroxy-Efavirenz, in HIV Patients.Antimicrobial agents and chemotherapy · 2017Article
- Pharmacokinetic Considerations for Combining Antiretroviral Therapy, Direct-Acting Antiviral Agents for Hepatitis C Virus, and Addiction Treatment Medications.Clinical pharmacology in drug development · 2017Review
- HIV-1 Alters Intestinal Expression of Drug Transporters and Metabolic Enzymes: Implications for Antiretroviral Drug Disposition.Antimicrobial agents and chemotherapy · 2016Article
- Pharmacogenetic and pharmacokinetic aspects of CYP3A induction by efavirenz in HIV patients.The pharmacogenomics journal · 2013Article
- Clinical pharmacokinetics of antiretroviral drugs in older persons.Expert opinion on drug metabolism & toxicology · 2013Review
- Fundamentals of population pharmacokinetic modelling: validation methods.Clinical pharmacokinetics · 2012Review
Corrections and comments
- Erratum issued
Authors and funding
9 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundPharmacokinetic 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.
methodsAfter 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.
resultsEfavirenz 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 (V(2)/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. The increased V(2)/F in females resulted in a 2-fold longer elimination half-life than in males.
conclusionOn the basis of the findings of this analysis, we conclude that, apart from bodyweight-based differences, both HIV/AIDS disease and sex affect efavirenz pharmacokinetics in Ugandans. HIV/AIDS disease is associated with reduced relative bioavailability of efavirenz. We recommend that findings from healthy subject studies be confirmed in HIV/AIDS patients and that caution be applied in direct extrapolation of exposure data to the target patient population.
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