Biopharmaceutics & Drug Disposition 1998-07-01

Pharmacokinetics of intravenous luxabendazole in rabbits: influence of the enterohepatic circulation.

L Alvarez-Bujidos, A I Ortiz, I T Molina-Martínez, C Cubría, D Ordóñez

Index: Biopharm. Drug Dispos. 19(5) , 341-7, (1998)

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Abstract

Luxabendazole (LBZ) is a new benzimidazole carbamate chemotherapeutic agent, which has proved to be very effective against adult and immature stages of the major gastrointestinal nematodes, trematodes and cestodes. While information on the efficacy of LBZ in several animal species is available, there seems to be no published information describing the disposition kinetics in any of them. As a part of the clinical development of luxabendazole, the pharmacokinetics of a single intravenous dose was investigated in parasite-free rabbits. Serial blood samples were collected at timed intervals for 12 h following administration of the dose, and concentrations in plasma were determined by a sensitive and specific HPLC method. Published data on LBZ point to the possible existence of an enterohepatic cycle (EHC), and so, it seemed appropriate to carry out two different forms of test. In the first, the possibility of intestinal reabsorption of LBZ excreted via the bile was allowed for (Treatment 1), while in the second it was interrupted by the oral administration of activated charcoal (Treatment 2). In both cases the animals were given a single dose of 10 mg kg-1 of LBZ intravenously (i.v). Comparison of the areas under the curve (AUCs) of LBZ concentrations in plasma samples taken from the animals receiving each treatment showed significant difference (p < 0.05). The given dose (10 mg kg-1) was converted in Treatment 1 to an effective dose of 13.9 mg kg-1 through recycling of LBZ. With Treatment 2 a bicompartmental distribution model for this drug was confirmed, together with high apparent distribution volumes: Vc = 1.87 L kg-1, and V beta = 7.09 L kg-1.