Effect of rifampicin-based antitubercular therapy on nevirapine plasma concentrations in South African adults with HIV-associated tuberculosis.
AffiliationDivision of Clinical Pharmacology, Department of Medicine, University of Cape Town, South Africa. firstname.lastname@example.org
MetadataShow full item record
AbstractBACKGROUND AND OBJECTIVES: Nevirapine-containing antiretroviral therapy (ART) and rifampicin-based antitubercular therapy are commonly co-administered in Africa, where nevirapine is often the only available non-nucleoside reverse transcriptase inhibitor. Rifampicin induces the metabolism of nevirapine, but the extent of the reduction in nevirapine concentrations has varied widely in previous studies. We describe the steady-state pharmacokinetics of nevirapine during and after antitubercular therapy in South African patients. METHODS: Sixteen patients receiving ART including standard doses of nevirapine were admitted twice for intensive pharmacokinetic sampling: during and after rifampicin-based antitubercular therapy. RESULTS: Geometric mean ratios for nevirapine pharmacokinetic parameters during versus after antitubercular therapy were 0.61 [90% confidence interval (CI) 0.49-0.79] for Cmax, 0.64 (90% CI 0.52-0.80) for area under the curve up to 12 h (AUC(0-12)) and 0.68 (90% CI 0.53-0.86) for Cmin. Nevirapine Cmin was subtherapeutic (<3 mg/L) in six patients during antitubercular therapy (one of whom developed virological failure) and in none afterwards. There was no correlation between rifampicin concentrations and the degree of nevirapine induction assessed by the proportional change in nevirapine concentrations between the two admissions. The ratio of nevirapine AUC(0-12) to the AUC(0-12) of its 12-hydroxy metabolite was significantly lower in the presence of antitubercular therapy, consistent with induced metabolism. CONCLUSIONS: Nevirapine concentrations were significantly decreased by concomitant rifampicin-based antitubercular therapy and a high proportion of patients had subtherapeutic plasma concentrations. Further study in African patients is required to determine the implications for treatment outcomes.
DescriptionTo access this article, click on "Additional Links".
- Plasma nevirapine levels and 24-week efficacy in HIV-infected patients receiving nevirapine-based highly active antiretroviral therapy with or without rifampicin.
- Authors: Manosuthi W, Sungkanuparph S, Thakkinstian A, Rattanasiri S, Chaovavanich A, Prasithsirikul W, Likanonsakul S, Ruxrungtham K
- Issue date: 2006 Jul 15
- Nevirapine levels after discontinuation of rifampicin therapy and 60-week efficacy of nevirapine-based antiretroviral therapy in HIV-infected patients with tuberculosis.
- Authors: Manosuthi W, Ruxrungtham K, Likanonsakul S, Prasithsirikul W, Inthong Y, Phoorisri T, Sungkanuparph S
- Issue date: 2007 Jan 1
- Outcomes of nevirapine- and efavirenz-based antiretroviral therapy when coadministered with rifampicin-based antitubercular therapy.
- Authors: Boulle A, Van Cutsem G, Cohen K, Hilderbrand K, Mathee S, Abrahams M, Goemaere E, Coetzee D, Maartens G
- Issue date: 2008 Aug 6
- Pharmacokinetics and 48-week efficacy of nevirapine: 400 mg versus 600 mg per day in HIV-tuberculosis coinfection receiving rifampicin.
- Authors: Avihingsanon A, Manosuthi W, Kantipong P, Chuchotaworn C, Moolphate S, Sakornjun W, Gorowara M, Yamada N, Yanai H, Mitarai S, Ishikawa N, Cooper DA, Phanuphak P, Burger D, Ruxrungtham K
- Issue date: 2008
- Effectiveness and safety of antiretrovirals with rifampicin: crucial issues for high-burden countries.
- Authors: Maartens G, Decloedt E, Cohen K
- Issue date: 2009