Pharmacokinetics of efavirenz (EFV) alone and in combination therapy with nelfinavir (NFV) in HIV‐1 infected patients

AIMS: To define the pharmacokinetic profile of efavirenz (EFV) in HIV-1 infected patients, when administered alone or with nelfinavir (NFV). METHODS: Eleven HIV-positive patients, in steady-state treatment with EFV and 11 patients in steady-state treatment with EFV+NFV, were evaluated. Blood samples for pharmacokinetic analysis were obtained during a dosage interval. Plasma concentrations of EFV were determined by h.p.l.c. RESULTS: No significant difference was found between the principal pharmacokinetic parameters of EFV when administered alone or in combination with NFV (mean AUC: 57.1-7727.3 vs 60.9+/-12.3 microg ml-1 h; mean CL/F: 0.18+/-0.072 vs 0.16+/-0.04 l h-1 kg-1; mean Cmax: 4.0+/-1.7 vs 4.3+/-1.2 microg ml-1, and mean tmax: 4.1+/-1.7 vs 3.5+/-0.5 h) Mean trough plasma concentrations (C0) of EFV were 1.64+/-0.93 microg ml-1, with and without NFV. A good correlation was found between C0 and AUC(0,24h) (r=0.96; P<0. 01). CONCLUSIONS: Despite the common metabolic pathway, there was no significant influence of NFV on the pharmacokinetics of EFV. EFV exhibits a relatively low interindividual variability and a dosing regimen of 600 mg day-1 assures plasma concentrations that are adequate for inhibition of viral replication.