Effect of efavirenz on the pharmacokinetics of ketoconazole in HIV-infected patients.
OBJECTIVE
To investigate the effect of efavirenz on the ketoconazole pharmacokinetics in HIV-infected patients.


METHODS
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.


RESULTS
Pretreatment with efavirenz significantly increased the clearance of ketoconazole by 201%. C(max) and AUC(0-24) were significantly decreased by 44 and 72%, respectively. The T ((1/2)) was significantly shorter by 58%.


CONCLUSIONS
Efavirenz has a strong inducing effect on the metabolism of ketoconazole.
Sriwiriyajan
Somchai
S
Department of Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla 90110, Thailand. srsomcha@medicine.psu.ac.th
Mahatthanatrakul
Werawath
W
Ridtitid
Wibool
W
Jaruratanasirikul
Sutep
S
D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy; D000328:Adult; D000480:Alkynes; D019380:Anti-HIV Agents / Q000494:pharmacology*; D000935:Antifungal Agents / Q000493:pharmacokinetics*; D019540:Area Under Curve; D048588:Benzoxazines / Q000494:pharmacology*; D002180:Candidiasis, Oral / Q000150:complications / Q000188:drug therapy; D003521:Cyclopropanes; D004347:Drug Interactions; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy; D006207:Half-Life; D006801:Humans; D007654:Ketoconazole / Q000493:pharmacokinetics*; D019259:Lamivudine; D008297:Male; D008875:Middle Aged; D018119:Stavudine
D000480:Alkynes; D019380:Anti-HIV Agents; D000935:Antifungal Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D019259:Lamivudine; D018119:Stavudine; C098320:efavirenz; D007654:Ketoconazole