Disposition of netobimin, albendazole, and its metabolites in the pregnant rat: developmental toxicity

Toxicology and Applied Pharmacology
C CristòfolM Arboix

Abstract

Netobimin (NTB), a benzimidazole prodrug with a good anthelmintic spectrum, was administered orally to female rats at a dose of 59.5 mg NTB/kg, to study its pharmacokinetic behavior and the disposition of its most important metabolites, albendazole (ABZ), albendazole sulfoxide (ABZSO), and albendazole sulfone (ABZSO2). ABZ was found in plasma after 6 hr. Peak plasma concentrations (Cmax) and areas under curves (AUC) of ABZSO were eight- and fourfold higher, respectively, than those of ABZSO2. To study NTB disposition in pregnant rats, three different drug doses (50, 59.5, and 70.7 mg/kg) were given. No significant differences were found between plasma concentrations for each metabolite at the three doses studied. Only ABZ concentrations rose slightly as dose increased. ABZ, ABZSO, and ABZSO2 were found in amniotic sacs and embryos at concentrations that were higher than plasma at the same times. The fetuses obtained after administration of each of the doses of NTB were studied to detect developmental toxicity. A significant correlation was found between rate of developmental toxicity and metabolite concentration. ABZSO embryo concentrations could be the main factor accounting for toxicity.

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Citations

Jun 21, 2011·Reproductive Toxicology·Gunnar CarlssonAgneta Oskarsson
Jul 31, 2003·Journal of Veterinary Pharmacology and Therapeutics·J VelíkJ Lamka
Jul 3, 2002·The Veterinary Journal·B P S CapeceC Cristòfol
Jul 4, 2002·The American Journal of Gastroenterology·Henry MontesDavid L Carr-Locke
Jun 13, 2018·Journal of Veterinary Pharmacology and Therapeutics·Laura MorenoLuis I Álvarez
Jul 7, 2018·Journal of Veterinary Research·Lidia RadkoSylwia Stypuła-Tręba
Oct 31, 2020·Journal of Medicinal Chemistry·Kevin A ScottJon T Njardarson
Aug 24, 1999·Reproductive Toxicology·M NavarroJ Ruberte

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Anthelmintics (ASM)

Anthelmintics or antihelminthics are a group of antiparasitic drugs that expel parasitic worms (helminths) and other internal parasites from the body by either stunning or killing them and without causing significant damage to the host. Discover the latest research on anthelmintics here.

Anthelmintics

Anthelmintics or antihelminthics are a group of antiparasitic drugs that expel parasitic worms (helminths) and other internal parasites from the body by either stunning or killing them and without causing significant damage to the host. Discover the latest research on anthelmintics here.

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