Efavirenz-induced decrease in plasma amprenavir levels in human immunodeficiency virus-infected patients and correction by ritonavir

• Published in: Antimicrobial agents and chemotherapy Vol. 44; no. 9; p. 2593
• Main Authors: Duval, X, Le Moing, V, Longuet, C, Leport, C, Vildé, J L, Lamotte, C, Peytavin, G, Farinotti, R
• Format: Journal Article
• Language: English
• Published: United States American Society for Microbiology 01-09-2000
• Subjects: Amprenavir; Anti-HIV Agents; Anti-HIV Agents - blood; Anti-HIV Agents - pharmacology; Anti-HIV Agents - therapeutic use; Aryl Hydrocarbon Hydroxylases; Benzoxazines; Carbamates; Commented On; Cytochrome P-450 CYP3A; Cytochrome P-450 Enzyme Inhibitors; Drug Interactions; Drug Therapy, Combination; Efavirenz; HIV Infections; HIV Infections - blood; HIV Infections - drug therapy; Human immunodeficiency virus 1; Humans; Letters to the Editor; Oxazines; Oxazines - pharmacology; Oxazines - therapeutic use; Oxidoreductases, N-Demethylating - antagonists & inhibitors; Protease; Ritonavir; Ritonavir - pharmacology; Ritonavir - therapeutic use; Sulfonamides; Sulfonamides - blood; Sulfonamides - therapeutic use
• ISSN: 0066-4804; 1098-6596
• DOI: 10.1128/AAC.44.9.2593-2593.2000

Drug interactions responsible for suboptimal drug exposure can lead to anti-human immunodeficiency virus (anti-HIV) treatment failure. Amprenavir (APV) is an HIV protease inhibitor with 90% inhibitory concentrations of 40 and 250 ng/ml without and with 50% human serum, respectively; its mean trough plasma level (daily dose of 1,200 mg twice a day [b.i.d.]) is 250 plus or minus 200 ng/ml. Efavirenz (EFV), a nonnucleoside reverse transcriptase inhibitor induces cytochromes P450-3A (CYP3A) and decreases dramatically plasma APV trough levels in half of the patients. We analyzed sequentially the APV-EFV interaction in seven HIV-infected patients.