title: Effect of ritonavir on the pharmacokinetics of the benzimidazoles albendazole and mebendazole: an interaction study in healthy volunteers.
abstract: BACKGROUND
  Benzimidazoles are often used concomitantly with protease inhibitors in patients with helminthic disease and HIV infection. Low bioavailability and extensive first-pass metabolism make benzimidazoles prone to pharmacokinetic drug interactions. The aim of the present study was to investigate potential drug interactions between the benzimidazoles albendazole and mebendazole and the potent CYP3A4 inhibitor ritonavir.
  
  
  METHODS
  Sixteen healthy volunteers were administered a single oral dose of 1,000 mg mebendazole or 400 mg albendazole (2 x n = 8). AUC, C(max), and t(1/2) of mebendazole, albendazole, and albendazole sulfoxide were studied in absence and after short-term (2 doses) and long-term (8 days) treatment with ritonavir 200 mg bid.
  
  
  RESULTS
  Pharmacokinetic parameters of albendazole and mebendazole were not changed by short-term administration of ritonavir. However, long-term administration of ritonavir resulted in significant changes in albendazole and mebendazole disposition, with a significant decrease in AUC(0-24) (27 and 43% of baseline for albendazole and mebendazole, respectively) and C(max) (26 and 41% of baseline, respectively).
  
  
  CONCLUSIONS
  The AUC(0-24) of benzimidazoles decreased after long-term use of ritonavir, while no changes in pharmacokinetic profiles were observed under short-term administration. These findings might help to optimize benzimidazole efficacy when used in combination with protease inhibitors.
authors: Division of Clinical Pharmacology and Toxicology, University Hospital Zurich, Rämistrasse 100, 8091 Zurich, Switzerland. natascia.corti@usz.ch
authors: Natascia
authors: N
authors: Corti
authors: Antje
authors: A
authors: Heck
authors: Katharina
authors: K
authors: Rentsch
authors: Walter
authors: W
authors: Zingg
authors: Alexander
authors: A
authors: Jetter
authors: Bruno
authors: B
authors: Stieger
authors: Christiane
authors: C
authors: Pauli-Magnus
mesh_terms: D000328:Adult; D015766:Albendazole / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D019380:Anti-HIV Agents / Q000494:pharmacology; D000977:Antiparasitic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D004347:Drug Interactions; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008463:Mebendazole / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D008875:Middle Aged; D012016:Reference Values; D019438:Ritonavir / Q000008:administration & dosage / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D019380:Anti-HIV Agents; D000977:Antiparasitic Agents; D017320:HIV Protease Inhibitors; D008463:Mebendazole; D015766:Albendazole; D019438:Ritonavir