A population approach to study the influence of nevirapine administration on lopinavir pharmacokinetics in HIV-1 infected patients.
OBJECTIVE
The influence of nevirapine (NVP) on lopinavir (LPV) pharmacokinetics was investigated by a population analysis based on a non-linear mixed-effect modelling method.


METHODS
In this analysis, 95 HIV-1 infected patients were studied [52 treated with LPV/ritonavir (400/100 mg twice a day) plus nucleoside reverse transcriptase inhibitors (group A), 22 patients treated with LPV/ritonavir (533.3/133.3 mg twice a day) plus NVP (group B) and 21 patients treated with LPV/ritonavir (400/100 mg twice a day) plus NVP (group C)].


RESULTS
The apparent clearance of LPV [mean+/-SD: 4.56+/-3.94 l h(-1) (group A) versus 7.14+/-1.77 l h(-1) (group B) versus 7.74+/-1.45 l h(-1) (group C)] was significantly (P <0.001) increased by the presence of NVP in the antiretroviral regimen and the mean trough plasma concentration of LPV was reduced in group C relative to group A [mean+/-SD: 2.23+/-1.35 mg/l versus 5.29+/-2.19 mg/l (P < 0.001)].


CONCLUSIONS
These results suggest an induction of LPV metabolism by NVP.
Dailly
Eric
E
Laboratoire de Pharmacologie clinique, Clinical Pharmacology Department, Hôtel Dieu, 9 Quai Moncousu, 44093, Nantes Cedex, France. eric.dailly@chu-nantes.fr
Reliquet
Véronique
V
Raffi
François
F
Jolliet
Pascale
P
D000328:Adult; D019380:Anti-HIV Agents / Q000493:pharmacokinetics*; D001499:Bayes Theorem; D004347:Drug Interactions; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D061466:Lopinavir; D008297:Male; D019829:Nevirapine / Q000494:pharmacology*; D011744:Pyrimidinones / Q000493:pharmacokinetics*; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology*
D019380:Anti-HIV Agents; D011744:Pyrimidinones; D018894:Reverse Transcriptase Inhibitors; D061466:Lopinavir; D019829:Nevirapine