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 infe cted patients, when administered alone or with nelfinavir (NFV). Methods Eleven HIV-positive patients, in steady-state treatment with EFV an d 11 patients in steady-state treatment with EFV+NFV, were evaluated. Blood samples for pharmacokinetic analysis were obtained during a dosage interva l. Plasma concentrations of EFV were determined by h.p.l.c. Results No significant difference was found between the principal pharmacok inetic parameters of EFV when administered alone or in combination with NFV (mean AUG: 57.1-7727.3 vs 60.9 +/- 12.3 mu g ml(-1) h; mean CL/F: 0.18 +/- 0.072 vs 0.16 +/- 0.04 l h(-1) kg(-1) mean C-max: 4.0 +/- 1.7 vs 4.3 +/- 1 .2 mu g ml(-1), and mean t(max): 4.1 +/- 1.7 vs 3.5 +/- 0.5 h) Mean trough plasma concentrations (CO) of EFV were 1.64 +/- 0.93 mu g ml(-1), with and without NFV. A good correlation was found between CO 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) assu res plasma concentrations that are adequate for inhibition of viral replica tion.