Sutep Jaruratanasirikul1, Somchai Sriwiriyajan. 1. Department of Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkla 90110, Thailand. jasutep@medicine.psu.ac.th
Abstract
OBJECTIVE: To investigate the drug interaction potential between itraconazole and nevirapine. METHODS: Our study was conducted in 12 healthy volunteers in two phases. In phase 1 (from days 1-28), all subjects were randomly assigned to a two-way crossover study of a nevirapine regimen (nevirapine 200 mg once daily for 7 days) and an itraconazole regimen (itraconazole 200 mg once daily for 7 days) with a 14-day wash-out period between. Phase 2 (from days 43-49) was performed 14 days after phase 1 ended, and all subjects received a combination regimen (nevirapine 200 mg combined with itraconazole 200 mg once daily for 7 days). Nevirapine pharmacokinetic studies were carried out starting with the seventh dose of nevirapine in the nevirapine regimen (on days 7-10 or 28-31) and the combination regimen (on days 49-52). Itraconazole pharmacokinetic studies were carried out starting with the seventh dose of itraconazole in the itraconazole regimen (on days 7-10 or 28-31) and the combination regimen (on days 49-52). RESULTS: There was no significant difference in nevirapine pharmacokinetic parameters between the nevirapine and combination regimens. Itraconazole plasma concentrations were lower when it was administered in the combination regimen than when it was administered in the itraconazole regimen. The mean C(max), AUC(0-96) and t (1/2) of itraconazole were significantly reduced by 38, 61 and 31%, respectively. CONCLUSION:Nevirapine had a strong inducing effect on the metabolism of itraconazole, but there was no significant effect of itraconazole on the pharmacokinetics of nevirapine. However, a higher daily dosage of itraconazole might have an inhibitory effect.
RCT Entities:
OBJECTIVE: To investigate the drug interaction potential between itraconazole and nevirapine. METHODS: Our study was conducted in 12 healthy volunteers in two phases. In phase 1 (from days 1-28), all subjects were randomly assigned to a two-way crossover study of a nevirapine regimen (nevirapine 200 mg once daily for 7 days) and an itraconazole regimen (itraconazole 200 mg once daily for 7 days) with a 14-day wash-out period between. Phase 2 (from days 43-49) was performed 14 days after phase 1 ended, and all subjects received a combination regimen (nevirapine 200 mg combined with itraconazole 200 mg once daily for 7 days). Nevirapine pharmacokinetic studies were carried out starting with the seventh dose of nevirapine in the nevirapine regimen (on days 7-10 or 28-31) and the combination regimen (on days 49-52). Itraconazole pharmacokinetic studies were carried out starting with the seventh dose of itraconazole in the itraconazole regimen (on days 7-10 or 28-31) and the combination regimen (on days 49-52). RESULTS: There was no significant difference in nevirapine pharmacokinetic parameters between the nevirapine and combination regimens. Itraconazole plasma concentrations were lower when it was administered in the combination regimen than when it was administered in the itraconazole regimen. The mean C(max), AUC(0-96) and t (1/2) of itraconazole were significantly reduced by 38, 61 and 31%, respectively. CONCLUSION:Nevirapine had a strong inducing effect on the metabolism of itraconazole, but there was no significant effect of itraconazole on the pharmacokinetics of nevirapine. However, a higher daily dosage of itraconazole might have an inhibitory effect.
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