Effect of efavirenz on the pharmacokinetics of ketoconazole in HIV-infected patients.

Somchai Sriwiriyajan, Werawath Mahatthanatrakul, Wibool Ridtitid, Sutep Jaruratanasirikul

Journal: European journal of clinical pharmacology 2007;63(5):479-83

PMID: 17345073

Abstract

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%.

CONCLUSION

Efavirenz has a strong inducing effect on the metabolism of ketoconazole.

Address: Department of Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla 90110, Thailand. [email protected]

DOI: 10.1007/s00228-007-0282-8

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https://dx.doi.org/10.1007/s00228-007-0282-8

MeSH Terms: AIDS-Related Opportunistic Infections, Adult, Alkynes, Anti-HIV Agents, Antifungal Agents, Area Under Curve, Benzoxazines, Candidiasis, Oral, Cyclopropanes, Drug Interactions, Female, HIV Infections, Half-Life, Humans, Ketoconazole, Lamivudine, Male, Middle Aged, Stavudine