Clinical Pharmacokinetics and the Impact of Genetic Polymorphism on a CYP2C19 Substrate, BMS-823778, in Healthy Subjects

• Published in: Drug metabolism and disposition Vol. 46; no. 3; pp. 316 - 325
• Main Authors: Gong, Jiachang, Hansen, Lars, Iacono, Lisa
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.03.2018; American Society for Pharmacology and Experimental Therapeutics, Inc
• Subjects: Absorption; Adolescent; Adult; Cytochrome P-450 CYP2C19 - genetics; Cytochrome P-450 CYP3A - genetics; Double-Blind Method; Excretion; Exposure; Gene polymorphism; Genotype; Glucocorticoids; Healthy Volunteers; Humans; Male; Metabolic disorders; Metabolism; Middle Aged; Pharmacokinetics; Pharmacology; Phenotype; Phenotypes; Polymorphism; Polymorphism, Genetic - genetics; Pyridines - pharmacokinetics; Statistical analysis; Substrates; Triazoles - pharmacokinetics; Young Adult; LLOQ; AE; IM; ADME; AI; EM; CLT; AUC; LC-MS/MS; MAD; SAD; 11β-HSD1; PM

BMS-823778 is a potent and selective inhibitor of 11β-HSD1, an enzyme that regulates tissue-specific intracellular glucocorticoid metabolism and is a compelling target for the treatment of metabolic diseases. Metabolism of BMS-823778 was mediated mainly by polymorphic CYP2C19, with minor contributio...