Your browser doesn't support javascript.
loading
Effect of a single cyclosporine dose on the single-dose pharmacokinetics of sitagliptin (MK-0431), a dipeptidyl peptidase-4 inhibitor, in healthy male subjects.
Krishna, Rajesh; Bergman, Arthur; Larson, Patrick; Cote, Josee; Lasseter, Kenneth; Dilzer, Stacey; Wang, Amy; Zeng, Wei; Chen, Li; Wagner, John; Herman, Gary.
Afiliação
  • Krishna R; Department of Clinical Pharmacology, Merck Research Laboratories, Merck & Co, Inc, 126 East Lincoln Avenue, Rahway, NJ 07065, USA. rajesh_krishna@merck.com.
J Clin Pharmacol ; 47(2): 165-74, 2007 Feb.
Article em En | MEDLINE | ID: mdl-17244767
Sitagliptin (MK-0431) is an orally active, potent, and selective dipeptidyl peptidase-4 inhibitor used for the treatment of patients with type 2 diabetes mellitus. Sitagliptin has been shown to be a substrate for P-glycoprotein in preclinical studies. Cyclosporine was used as a probe P-glycoprotein inhibitor at a high dose to evaluate the potential effect of potent P-glycoprotein inhibition on single-dose sitagliptin pharmacokinetics in healthy male subjects. Eight healthy young men received a single oral 600-mg dose of cyclosporine with a single 100-mg oral sitagliptin dose and a single oral 100-mg sitagliptin dose alone in an open-label, randomized, 2-period, crossover study. Single doses of sitagliptin with or without single doses of cyclosporine were generally well tolerated. The sitagliptin AUC(0-infinity) geometric mean ratio was 1.29 with a 90% confidence interval of (1.24, 1.34). The sitagliptin Cmax geometric mean ratio was 1.68 with a 90% confidence interval of (1.35, 2.08). Cyclosporine coadministration did not appear to affect apparent sitagliptin renal clearance, t(1/2), or C(24 h), suggesting that effects of these high doses of cyclosporine are more likely due to enhanced absorption of sitagliptin, potentially through inhibition of intestinal P-glycoprotein. These results rationalize the use of a single high-dose cyclosporine as a probe inhibitor of P-glycoprotein for compound candidates whose elimination is less dependent on CYP3A4-mediated metabolism.
Assuntos
Buscar no Google
Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Pirazinas / Triazóis / Ciclosporina / Membro 1 da Subfamília B de Cassetes de Ligação de ATP Tipo de estudo: Clinical_trials Limite: Adult / Humans / Male Idioma: En Ano de publicação: 2007 Tipo de documento: Article
Buscar no Google
Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Pirazinas / Triazóis / Ciclosporina / Membro 1 da Subfamília B de Cassetes de Ligação de ATP Tipo de estudo: Clinical_trials Limite: Adult / Humans / Male Idioma: En Ano de publicação: 2007 Tipo de documento: Article