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)]. Conclusion: These results suggest an induction of LPV metabolism by NVP.