title: Effect of faldaprevir on raltegravir pharmacokinetics in healthy volunteers.
abstract: Faldaprevir is a potent hepatitis C virus (HCV) NS3/4A protease inhibitor and an inhibitor of UDP-glucuronosyltransferase-1A1 (UGT1A1), which is involved in raltegravir clearance. Raltegravir, an HIV integrase inhibitor, may be used in combination with HCV treatment in HCV/HIV co-infected patients. In this open-label, 2-period, fixed-sequence study, 24 healthy volunteers (12 males) received faldaprevir 240 mg and raltegravir 400 mg in 2 treatment schedules (A and B) separated by a washout phase of ≥7 days: (A) twice-daily raltegravir (Days 1-3), once-daily raltegravir (Day 4); (B) twice-daily raltegravir and twice-daily faldaprevir (loading dose, Day 1), twice-daily raltegravir and once-daily faldaprevir (Days 2-5), once-daily raltegravir and once-daily faldaprevir (Day 6). Pharmacokinetics and safety were assessed over 132 hours post-dosing. Compared with raltegravir alone, co-administration with faldaprevir led to 2.7-fold and 2.5-fold increases in raltegravir geometric mean AUC(τ,ss) and C(max,ss), respectively, and a similar increase in raltegravir glucuronide metabolite exposure. No serious adverse events (AEs) were reported and no subject discontinued due to AEs. Faldaprevir and raltegravir co-administration was well tolerated and resulted in a moderate increase in raltegravir exposure.
authors.affiliation: Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, USA.
authors.forename: David
authors.initials: D
authors.lastname: Joseph
authors.forename: Peter
authors.initials: P
authors.lastname: Rose
authors.forename: Natalja
authors.initials: N
authors.lastname: Strelkowa
authors.forename: Armin
authors.initials: A
authors.lastname: Schultz
authors.forename: Jeanette
authors.initials: J
authors.lastname: Garcia
authors.forename: Mabrouk
authors.initials: M
authors.lastname: Elgadi
authors.forename: Fenglei
authors.initials: F
authors.lastname: Huang
mesh_terms: D000328:Adult; D000621:Aminoisobutyric Acids; D004334:Drug Administration Schedule; D004347:Drug Interactions / Q000235:genetics; D005260:Female; D005838:Genotype; D014453:Glucuronosyltransferase / Q000235:genetics; D019428:HIV Integrase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D064368:Healthy Volunteers; D006801:Humans; D007930:Leucine / Q000031:analogs & derivatives; D008297:Male; D009842:Oligopeptides / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D011392:Proline / Q000031:analogs & derivatives; D011480:Protease Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D011804:Quinolines; D000068898:Raltegravir Potassium / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D013844:Thiazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D055815:Young Adult; D000099148:UGT1A1 Enzyme
chemical_list: D000621:Aminoisobutyric Acids; D014453:Glucuronosyltransferase; D019428:HIV Integrase Inhibitors; D007930:Leucine; D009842:Oligopeptides; D011392:Proline; D011480:Protease Inhibitors; D011804:Quinolines; D000068898:Raltegravir Potassium; D013844:Thiazoles; D000099148:UGT1A1 Enzyme; C552340:faldaprevir
keywords: HIV/AIDS; clinical trials; drug interactions; infectious diseases; pharmacokinetics and drug metabolism; virology