title: Multiple-dose pharmacokinetics of efavirenz with and without the use of rifampicin in HIV-positive patients.
abstract: 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/microl and 5.2 /microl, respectively. Cases had a significantly higher Cl/F/kg if compared with controls (0.269 +/- 0.12 versus 0.167 + 0.05 L/h/kg, p<0.01). Otherwise, dose-dependent pharmacokinetic parameters of EFV were similar between cases and controls. Interindividual variability was consistently higher among TB cases compared to controls for all considered parameters. All cases completed combined treatment and no increased EFV toxicity was observed. These results suggest that a dose of 800 mg of EFV in association with rifampicin may be appropriate for patients of weight > 60 kg in Europe. Therapeutic drug monitoring may be beneficial for patients on combination therapy with RIF.
authors.affiliation: Institute of Infectious and Tropical Diseases, University of Brescia, Brescia, Italy. amatteelli@bsnet.it
authors.forename: Alberto
authors.initials: A
authors.lastname: Matteelli
authors.forename: Mario
authors.initials: M
authors.lastname: Regazzi
authors.forename: Paola
authors.initials: P
authors.lastname: Villani
authors.forename: Giuseppina
authors.initials: G
authors.lastname: De Iaco
authors.forename: Maria
authors.initials: M
authors.lastname: Cusato
authors.forename: Anna Cristina C
authors.initials: AC
authors.lastname: Carvalho
authors.forename: Silvio
authors.initials: S
authors.lastname: Caligaris
authors.forename: Lina
authors.initials: L
authors.lastname: Tomasoni
authors.forename: Maria
authors.initials: M
authors.lastname: Manfrin
authors.forename: Susanna
authors.initials: S
authors.lastname: Capone
authors.forename: Giampiero
authors.initials: G
authors.lastname: Carosi
mesh_terms: D000328:Adult; D000480:Alkynes; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000904:Antibiotics, Antitubercular / Q000493:pharmacokinetics*; D048588:Benzoxazines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001682:Biological Availability; D003521:Cyclopropanes; D004347:Drug Interactions; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D008297:Male; D011446:Prospective Studies; D012293:Rifampin / Q000493:pharmacokinetics*; D014376:Tuberculosis / Q000150:complications / Q000188:drug therapy*
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D000904:Antibiotics, Antitubercular; D048588:Benzoxazines; D003521:Cyclopropanes; C098320:efavirenz; D012293:Rifampin