Darunavir: a second-generation protease inhibitor.

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Busse KH, Penzak SR

Darunavir: a second-generation protease inhibitor.

Am J Health Syst Pharm. 2007 Aug 1;64(15):1593-602. doi: 10.2146/ajhp060668.

PubMed ID

17646561 [ View in PubMed

]

Abstract

PURPOSE: The pharmacology, pharmacokinetics, drug interactions, clinical efficacy, adverse events, dosage and administration, and place in therapy of darunavir are reviewed. SUMMARY: Darunavir is the most recent protease inhibitor (PI) to receive approved labeling from the Food and Drug Administration for the treatment of human immunodeficiency virus (HIV). Darunavir is unique among currently available PIs because it maintains antiretroviral activity against a variety of multidrug-resistant HIV strains. Darunavir is well absorbed, and the bioavailability of darunavir increases by 30% when given with food. Darunavir is approximately 95% bound to plasma proteins. Darunavir is metabolized by and inhibits cytochrome P-450 (CYP) isoenzyme 3A4; therefore, darunavir is prone to CYP3A4-mediated drug-drug interactions. Two trials have demonstrated the clinical efficacy of darunavir in HIV-positive patients previously treated with antiretrovirals. One trial demonstrated a 2 log(10) decrease in plasma HIV RNA levels, compared with a decrease of <1 log(10) in the control group. Average increases in CD4+ T-cell counts for darunavir and control groups were 124 and 20 cells/mm(3), respectively. Adverse events reported from preliminary safety data indicate that darunavir has a similar safety profile to other currently available PIs. The recommended adult dosage of darunavir is 600 mg (two tablets) combined with ritonavir 100 mg every 12 hours with food. Darunavir should be used with caution in patients with hepatic dysfunction. No dosage adjustment is necessary for patients with mild or moderate renal dysfunction. CONCLUSION: Darunavir is a new HIV PI that retains virological activity in the presence of multiple protease mutations. As such, darunavir appears to be a useful component of optimized combination antiretroviral therapy for HIV-infected patients previously treated with antiretrovirals.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Darunavir	Cytochrome P450 3A4	Protein	Humans	Unknown	Substrate Inhibitor	Details

Drug Interactions

Drugs	Interaction
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