Metabolic disposition of casopitant, a potent neurokinin-1 receptor antagonist, in mice, rats, and dogs

Drug Metabolism and Disposition : the Biological Fate of Chemicals
Lidia MiragliaMario Pellegatti

Abstract

Casopitant [1-piperidinecarboxamide,4-(4-acetyl-1-piperazinyl)-N-((1R)-1-(3,5-bis(trifluoromethyl)phenyl)-ethyl)-2-(4-fluoro-2-methylphenyl)-N-methyl-(2R,4S)] is a potent and selective antagonist of the neurokinin-1 (NK1) receptor, developed for the prevention of chemotherapy-induced nausea and vomiting and postoperative nausea and vomiting. Absorption, distribution, metabolism, and elimination of [(14)C]casopitant have been investigated in the mouse, rat, and dog after single oral administration and compared with those in humans. [(14)C]Casopitant was rapidly absorbed in all three species: the maximum plasma concentration of radioactivity was generally observed 0.5 to 2 h after a single oral dose. In dog and female rat, as observed for humans, the principal circulating radiolabeled components were unchanged casopitant and its hydroxylated derivative M13. In rats, there was an evident sex-related difference in the rate of elimination of drug-related material with elimination being more rapid in males than in females. In dogs and mice, no notable sex differences were observed in the pattern of excretion. The elimination of drug-related radioactivity was largely by metabolism, with metabolites excreted primarily in the feces. The...Continue Reading

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May 8, 2009·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Mario PellegattiBrendan M Johnson
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Citations

Mar 23, 2011·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Leslie D NagyLaura Lowe Furge
Jan 18, 2012·Expert Opinion on Drug Metabolism & Toxicology·Mario Pellegatti
Jan 19, 2011·Expert Opinion on Drug Metabolism & Toxicology·Mario Pellegatti, Sabrina Pagliarusco
Dec 1, 2011·Birth Defects Research. Part B, Developmental and Reproductive Toxicology·Mary K ZiejewskiApril R Apostoli
Oct 28, 2010·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Sabrina PagliaruscoMario Pellegatti
Sep 5, 2019·Pharmaceutics·Agnieszka Majkowska-PilipEwa Gniazdowska

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