Impact of nevirapine or efavirenz co-administration on ritonavir-boosted amprenavir pharmacokinetics in HIV-infected patients.
The influence of nevirapine or efavirenz co-administration on ritonavir-boosted amprenavir pharmacokinetics was investigated in HIV-infected patients with a population pharmacokinetic approach. The analysis was performed with a population of 61 patients treated with fosamprenavir/ritonavir (700 mg/100 mg twice daily) combined with nucleoside/nucleotide reverse transcriptase inhibitors +/- enfuvirtide and no other antiretroviral drugs (group A, n = 46) or nevirapine (group B, n = 10) or efavirenz (group C, n = 5). No significant increase in amprenavir clearance [mean +/- standard deviation: 22.49 +/- 10.32 (group A) vs. 21.57 +/- 9.62 (group B) vs. 20.15 +/- 5.18 (group C) L/h] and no significant decrease in trough amprenavir plasma concentrations [1.75 +/- 0.95 (group A) vs. 1.82 +/- 0.72 (group B) vs. 1.55 +/- 0.66 (group C) mg/L] were found in groups B and C in comparison with group A, although nevirapine and efavirenz are inductors of protease inhibitors metabolism. These results suggest that fosamprenavir/ritonavir should be used at standard doses of 700 mg/100 mg twice daily when combined with efavirenz or nevirapine.
Dailly
Eric
E
Laboratoire de Pharmacologie clinique, Clinical Pharmacology Department, 9 Quai Moncousu, 44093 Nantes Cedex, France. eric.dailly@chu-nantes.fr
Raffi
François
F
Biron
Charlotte
C
Allavena
C
C
Jolliet
P
P
D000328:Adult; D000480:Alkynes; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D001499:Bayes Theorem; D048588:Benzoxazines / Q000627:therapeutic use*; D002219:Carbamates / Q000097:blood* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D003521:Cyclopropanes; D004359:Drug Therapy, Combination; D005260:Female; D005602:France; D005663:Furans; D015658:HIV Infections / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D008297:Male; D008954:Models, Biological; D019829:Nevirapine / Q000627:therapeutic use*; D010755:Organophosphates / Q000493:pharmacokinetics* / Q000627:therapeutic use; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D019438:Ritonavir / Q000627:therapeutic use*; D013449:Sulfonamides / Q000097:blood* / Q000493:pharmacokinetics* / Q000627:therapeutic use
D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D002219:Carbamates; D003521:Cyclopropanes; D005663:Furans; D010755:Organophosphates; D018894:Reverse Transcriptase Inhibitors; D013449:Sulfonamides; C095108:amprenavir; D019829:Nevirapine; C098320:efavirenz; D019438:Ritonavir; C426859:fosamprenavir