Non-clinical evaluation of the metabolism, pharmacokinetics and excretion of S-777469, a new cannabinoid receptor 2 selective agonist.

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Sekiguchi K, Kanazu T, Takeuchi M, Hasegawa H, Yamaguchi Y

Non-clinical evaluation of the metabolism, pharmacokinetics and excretion of S-777469, a new cannabinoid receptor 2 selective agonist.

Xenobiotica. 2014 Jan;44(1):48-58. doi: 10.3109/00498254.2013.805853. Epub 2013 Jun 13.

PubMed ID

23763649 [ View in PubMed

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Abstract

1. The drug metabolism and pharmacokinetics of S-777469 were investigated in in vitro (rat, dog and human) and in in vivo (rats and dogs). 2. S-777469 was rapidly and well absorbed, with bioavailability values ranging from 50 to 70% in rats and dogs, almost all drug radioactivity was excreted into the feces via bile within 48 h. Thus, good pharmacokinetics of S-777469 (e.g. systemic exposure and excretion rate) would be anticipated in humans. 3. In vitro metabolism of S-777469 was qualitatively similar in rat, dog and human hepatocytes. S-777469 acyl glucuronide, S-777469 5-hydroxymethyl and S-777469 4-hydroxycyclohexane were the main metabolites in rats, dogs and humans. In vivo metabolism in rats and dogs showed good qualitative agreement with in vitro metabolism, and no metabolites exceeded 10% of total radioactivity in rat and dog plasma. 4. No unique metabolites were observed in human hepatocytes. Therefore, rats and dogs were thought to be appropriate species for non-clinical toxicity studies. 5. In conclusion, these data should be useful for the characterization of the pharmacokinetic properties of S-777469 and the estimation of its pharmacokinetic fate in humans.

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Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
S-777469	Cannabinoid receptor 2	Protein	Humans	Unknown	Agonist	Details