Multiple-dose pharmacokinetics of Efavirenz with and without the use of Rifampicin in HIV-positive patients

Rifampicin (RIF) decreases serum concentrations of several antiretroviral drugs. We carried out a prospective, comparative study to define efavirenz (EFV) pharmacokinetics in 16 cases and 13 controls. Cases were HIV and tuberculosis (TB) co-infected adults assuming RIF 600 mg once daily and EFV 800 mg once daily. Patients on EFV at standard 600 mg dose without RIF were taken as controls. EFV levels in plasma were assayed by high-performance liquid chromatography (HLPC) predose (C_trough) and at 1, 2, 3, 4, 5, 6, 8, 10, 11, 12, 13, 14, 16, 18, 22 and 24 hours post-dose, and pharmacokinetic parameters were determined by non-compartmental methods. Among cases, 81% were males, mean age was 37 years, 50% were Caucasians, mean weight was 64 kg, mean CD4 cell counts and log HIV RNA copies were 160/μ1 and 5.2/μ1, respectively. Cases had a significantly higher C1/F/kg if compared with controls (0.269 ± 0.12 versus 0.167 ± 0.05 L/h/kg, p 60 kg in Europe. Therapeutic drug monitoring may be beneficial for patients on combination therapy with RIF.