Co-administration of fluconazole increases nevirapine concentrations in HIV-infected Ugandans

Wakeham, K., Parkes-Ratanshi, R., Watson, V., Ggayi, A.-B., Khoo, S. and Lalloo, D. G. (2010) Co-administration of fluconazole increases nevirapine concentrations in HIV-infected Ugandans. Journal of Antimicrobial Chemotherapy, 65(2), pp. 316-319. (doi: 10.1093/jac/dkp451) (PMID:20032007) (PMCID:PMC2809247)

Abstract

Background: Data from retrospective studies have suggested that there may be an interaction between fluconazole and nevirapine, increasing nevirapine concentrations and potentially leading to hepatotoxicity.<p></p> Methods: This study was nested within a large double-blind placebo-controlled study designed to determine if primary prophylaxis with fluconazole (200 mg three times per week) could reduce cryptococcal disease [CRYPTOPRO (ISRCTN 76481529)] in HIV-infected adults in rural south-western Uganda. Detailed pharmacokinetic studies were performed on 49 participants (22 on placebo and 27 on fluconazole) who had been on fluconazole or placebo with nevirapine for ≥4 weeks.<p></p> Results: The geometric mean pre-dose concentrations of nevirapine were 3865 ng/mL [95% confidence interval (95% CI) 3452–4758 ng/mL] and 5141 ng/mL (95% CI 4760–6595 ng/mL) (<i>P</i> = 0.009) in the placebo and fluconazole arms, respectively. The change in the peak nevirapine concentration in plasma (C_max) was also higher in the fluconazole arm compared with the placebo arm [median 6546 (95% CI 6040–7974) versus 5126 (95% CI 4739–5773) ng/mL, <i>P</i> = 0.012]. Fluconazole increased the nevirapine area under the curve (AUC) from 0 to 8 h by 29% [geometric mean AUC_0–8 46 135 (95% CI 42 432–57 173) versus 35 871 (95% CI 32 808–41 372) ng•h/mL, <i>P</i> = 0.016]. In the larger cohort from which the participants were drawn, co-administration of fluconazole did not increase the risk of hepatotoxicity.<p></p> Conclusions: Fluconazole led to significant increases in nevirapine exposure, but was not associated with evidence of increased hepatotoxicity.<p></p>

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Wakeham, Dr Katie
• Authors: Wakeham, K., Parkes-Ratanshi, R., Watson, V., Ggayi, A.-B., Khoo, S., and Lalloo, D. G.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Journal of Antimicrobial Chemotherapy
• Publisher: Oxford University Press
• ISSN: 0305-7453
• ISSN (Online): 1460-2091
• Copyright Holders: Copyright © 2009 The Authors
• First Published: First published in Journal of Antimicrobial Chemotherapy 65(2):316-319
• Publisher Policy: Reproduced under a Creative Commons License