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dc.contributor.authorCohen, K
dc.contributor.authorVan Cutsem, G
dc.contributor.authorBoulle, A
dc.contributor.authorMcIlleron, H
dc.contributor.authorGoemaere, E
dc.contributor.authorSmith, P J
dc.contributor.authorMaartens, G
dc.date.accessioned2008-05-27T14:12:12Z
dc.date.available2008-05-27T14:12:12Z
dc.date.issued2008-02
dc.identifier.citationEffect of rifampicin-based antitubercular therapy on nevirapine plasma concentrations in South African adults with HIV-associated tuberculosis. 2008, 61 (2):389-93 J. Antimicrob. Chemother.en
dc.identifier.issn1460-2091
dc.identifier.pmid18096560
dc.identifier.doi10.1093/jac/dkm484
dc.identifier.urihttp://hdl.handle.net/10144/28297
dc.descriptionTo access this article, click on "Additional Links".en
dc.description.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.
dc.language.isoenen
dc.publisherOxford Journalsen
dc.relation.urlhttp://jac.oxfordjournals.org/cgi/content/full/61/2/389en
dc.rightsArchived on this site with kind permission from Oxford University Press and the British Society for Antimicrobial Chemotherapyen
dc.subject.meshAdulten
dc.subject.meshAntitubercular Agentsen
dc.subject.meshDrug Interactionsen
dc.subject.meshDrug Therapy, Combinationen
dc.subject.meshFemaleen
dc.subject.meshHIV Infectionsen
dc.subject.meshHIV-1en
dc.subject.meshHumansen
dc.subject.meshMaleen
dc.subject.meshNevirapineen
dc.subject.meshRifampinen
dc.subject.meshSouth Africaen
dc.subject.meshTuberculosisen
dc.titleEffect of rifampicin-based antitubercular therapy on nevirapine plasma concentrations in South African adults with HIV-associated tuberculosis.en
dc.contributor.departmentDivision of Clinical Pharmacology, Department of Medicine, University of Cape Town, South Africa. karen.cohen@uct.ac.zaen
dc.identifier.journalJournal of Antimicrobial Chemotherapyen
html.description.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.


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