Experience of a combination including indinavir 400 mg plus ritonavir 200 mg twice daily in HIV-infected patients: pharmacokinetic data.
Low doses of ritonavir, a strong inhibitor of cytochrome P450 3A4, enhances the pharmacokinetic profile of indinavir with increased serum levels. We assessed the indinavir-ritonavir 400/200 twice daily combination in 17 HIV-infected patients focusing on the pharmacokinetic data and the tolerance of this regimen. IDV trough and peak concentrations were measured by high-performance liquid chromatography. Median indinavir trough and peak concentrations were 553 ng/ml and 3626 ng/ml, respectively. A good tolerance was observed except for three patients who experienced a major toxicity. Only one dose adjustment was related to indinavir toxicity. Considering the fact that Cmax is mainly responsible of the adverse effects, particularly renal stones, the indinavir-ritonavir 400/200 mg twice daily regimen offers a well-tolerated combination with an increased Cmin but a lower Cmax compared with both the standard tid regimen and higher dose of IDV-RTV regimens.
Solas
C
C
Department of Pharmacokinetics and Toxicokinetics, Timone Hospital, 264, rue Saint-Pierre, 13385 cedex 05, Marseille, France. caro_salos@yahoo.fr
Petit
N
N
Orticoni
M
M
Durand
A
A
Gastaut
J A
JA
Lacarelle
B
B
D023241:Antiretroviral Therapy, Highly Active; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D015497:HIV-1 / Q000302:isolation & purification; D015498:HIV-2 / Q000302:isolation & purification; D006801:Humans; D019469:Indinavir / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008297:Male; D019438:Ritonavir / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D019562:Viral Load
D017320:HIV Protease Inhibitors; D019469:Indinavir; D019438:Ritonavir