Effect of efavirenz on the pharmacokinetics of ketoconazole in HIV-infected patients
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To investigate the effect of efavirenz on the ketoconazole pharmacokinetics in HIV-infected patients.
Twelve HIV-infected patients were assigned into a one-sequence, two-period pharmacokinetic interaction study. In phase one, the patients received 400 mg of ketoconazole as a single oral dose on day 1; in phase two, they received 600 mg of efavirenz once daily in combination with 150 mg of lamivudine and 30 or 40 mg of stavudine twice daily on days 2 to 16. On day 16, 400 mg of ketoconazole was added to the regimen as a single oral dose. Ketoconazole pharmacokinetics were studied on days 1 and 16.
Pretreatment with efavirenz significantly increased the clearance of ketoconazole by 201%. Cmax and AUC0−24 were significantly decreased by 44 and 72%, respectively. The T ½ was significantly shorter by 58%.
Efavirenz has a strong inducing effect on the metabolism of ketoconazole.
KeywordsDrug interaction Efavirenz Ketoconazole HIV-infected patients Pharmacokinetics
We acknowledge and appreciate the financial support of this study by the Prince of Songkla University and would like to thank to Miss Stefania Vignotto and Mr. David Brown for checking our English. The experiments comply with the current laws of the country in which we were performed.
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