1. H.p.l.c. analyses were performed to investigate the plasma kinetics of albendazole (ABZ), the sulphoxide (SO.ABZ) and sulphone (SO2ABZ) metabolites, as well as the chirality vs time of SO.ABZ, after oral administration to rats, dogs and man of prochiral sulphide antiparasitic drug ABZ. 2. In all three species the initial plasma concentration ratio of the enantiomers, as soon as SO.ABZ could be detected in plasma, was that of a racemate. 3. Subsequently, the ratio (+)/(-) increased linearly with time, reaching values of 13.1 and 9.3 in man and dogs, respectively, while it decreased to 0.6 in rats. 4. The (+) enantiomer represents 80%, 70% and 41% of the area under the curve of the total SO.ABZ in man, dogs and rats, respectively.
plasma clearance as a measure of glomerular filtration was determined in 31 dogs and 19 cats after an intravenous (IV) bolus injection. All animals were healthy and privately owned. Serial blood samples were taken before and up to 4 h after tracer injection. Iohexol plasma concentration was determined using X-ray fluorescence. A plasma tracer elimination curve was generated and clearance was calculated by dividing the injected dose by the area under the curve estimated using a two-compartment pharmacological model. Clearance was normalized to body weight (BW), body surface area (BSA), and extracellular fluid volume (ECFV). Mean, SD, and coefficient of variation of plasma clearance, before and after normalization, were calculated. Linear regression analyses were performed between body size and normalized plasma clearances. No significant linear relation was found between BSA and clearance normalized to BSA in dogs, and between BSA, BW, ECFV and clearance normalized to BSA, BW, and ECFV in cats. The optimal method for normalization of iohexol plasma clearance in dogs was by using BSA. In cats, all three methods tested were considered satisfactory. Normalization to BSA appears to be superior to normalization to BW and ECFV in dogs, and can be recommended for clinical use.
Two prochiral sulphide drugs, fenbendazole (FBZ) and albendazole (ABZ) were administered orally to sheep. Blood samples were analysed for parent drug and S-oxidation metabolites and the chirality of the sulphoxide metabolites was determined. The plasma concentrations of the enantiomers of the sulphoxides were never a racemate. On the contrary, the ratios were greater than 1 as soon as the sulphoxide compounds could be detected in plasma. They subsequently increased linearly throughout the time course of the kinetics, reaching the level 86:14 after FBZ and 95:5 after ABZ treatment. The major enantiomer represented 74% and 86% of the total AUC of SO.FBZ and SO.ABZ, respectively.
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