Pharmacokinetics and Short‐Term Safety of Etravirine in Combination With Fluconazole or Voriconazole in HIV‐Negative Volunteers

摘要: The nonnucleoside reverse transcriptase inhibitor etravirine, approved for use in treatment-experienced, HIV-1-infected patients, is a substrate and inducer of cytochrome P450 (CYP) 3A4 CYP2C9/CYP2C19. Pharmacokinetic interactions safety etravirine 200 mg twice daily coadministered with fluconazole or voriconazole daily, both inhibitors CYP3A4, CYP2C9, CYP2C19, were evaluated an open-label, randomized, 3-period crossover trial 18 HIV-negative volunteers. Based on least squares means (LSM) ratios, coadministration resulted higher exposures (area under plasma concentration-time curve from 0-12 hours [AUC(12) (h) ] 1.86- 1.36-fold, respectively). Fluconazole pharmacokinetics unchanged (AUC(12) LSM ratio: 0.94), concentrations slightly raised 1.14). All treatments combinations well tolerated, no grade 3 4 adverse events observed during treatment. There was 1 event-related withdrawal treatment alone (leukocyturia). most frequent headache blurred vision (11 8 volunteers, respectively), occurring exclusively voriconazole-alone between are not expected to be clinically relevant; dose adjustments required coadministration.