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Effect of ritonavir on the pharmacokinetics of the benzimidazoles albendazole and mebendazole: an interaction study in healthy volunteers

Corti, Natascia
Heck, Antje
Rentsch, Katharina
Jetter, Alexander
Stieger, Bruno
Pauli-Magnus, Christiane
Published in European Journal of Clinical Pharmacology. 2009, vol. 65, no. 10, p. 999-1006
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). CONCLUSION: 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.
Keywords AdultAlbendazole/administration & dosage/adverse effects/*pharmacokineticsAnti-HIV Agents/pharmacologyAntiparasitic Agents/administration & dosage/adverse effects/*pharmacokineticsDrug InteractionsHIV Protease Inhibitors/administration & dosage/*pharmacologyHumansMaleMebendazole/administration & dosage/adverse effects/*pharmacokineticsMiddle AgedReference ValuesRitonavir/administration & dosage/*pharmacologyTime Factors
PMID: 19562329
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CORTI, Natascia et al. Effect of ritonavir on the pharmacokinetics of the benzimidazoles albendazole and mebendazole: an interaction study in healthy volunteers. In: European Journal of Clinical Pharmacology, 2009, vol. 65, n° 10, p. 999-1006.

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Deposited on : 2012-04-23

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