Darunavir: pharmacokinetics and drug interactions.
Darunavir (TMC114) is a new HIV protease inhibitor that has demonstrated substantial antiretroviral activity against wild-type HIV-1 virus and multidrug-resistant strains. Darunavir inhibits and is primarily metabolized by cytochrome P450 3A (CYP3A) isoenzymes and is coadministered with low-dose ritonavir (darunavir/r); ritonavir is an inhibitor of CYP3A isoenzymes and pharmacologically enhances darunavir, resulting in increased plasma concentrations and allowing for a lower daily dose. The t1/2 (terminal elimination half-life) of darunavir is 15 h in the presence of ritonavir. An extensive darunavir/r drug-drug interaction programme has been undertaken, covering a wide range of therapeutic areas. Studies conducted in HIV-negative healthy volunteers and in HIV-infected patients show that the potential for interactions is well characterized and the interactions are manageable. For most drugs investigated, no dose adjustments of darunavir/r or the co-administered drug are required. This article reviews all the pharmacokinetic and drug-drug interaction studies conducted to date for darunavir/r, providing guidance on how to co-administer darunavir/r with many other antiretroviral or non-antiretroviral medications commonly used in HIV-infected individuals.
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David
D
Department of Pharmacology and Therapeutics, University of Liverpool, Liverpool, UK. daveback@liverpool.ac.uk
Sekar
Vanitha
V
Hoetelmans
Richard M W
RM
D000069454:Darunavir; D004347:Drug Interactions; D015658:HIV Infections / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000493:pharmacokinetics* / Q000494:pharmacology*; D006801:Humans; D013449:Sulfonamides / Q000493:pharmacokinetics* / Q000494:pharmacology*
D017320:HIV Protease Inhibitors; D013449:Sulfonamides; D000069454:Darunavir