title: Metabolism and disposition of the αv-integrin ß3/ß5 receptor antagonist cilengitide, a cyclic polypeptide, in humans.
abstract: Cilengitide (EMD 121974, manufactured by Merck KGaA, Darmstadt, Germany) is an αv-integrin receptor antagonist showing high affinity for αvβ3 and αvβ5.This study determined the mass balance of cilengitide in healthy volunteers receiving a single intravenous infusion of 2.1 MBq (14) C-cilengitide spiked into 250 mL of 2000 mg of cilengitide. Blood, urine, and feces were collected up to day 15 or until excretion of radioactivity was below 1% of the administered dose. Total radioactivity derived from the administration of (14) C-cilengitide and unlabeled cilengitide levels were determined and used for calculation of pharmacokinetic parameters.(14) C-cilengitide-related radioactivity was completely recovered (94.5%; 87.4%-100.6%) and was mainly excreted into urine (mean, 79.0%; range, 70.3%-88.2%) and to a lesser extent into feces (mean, 15.5%; range, 9.3%-20.3%). Of the administered dose, 77.5% was recovered as unchanged cilengitide in urine. The concentration profiles of cilengitide and total radioactivity in plasma were comparable. No circulating metabolites were identified in plasma and urine. Two metabolites,M606-1 and M606-2, were identified in feces considered to be formed by intestinal peptidases or by peptidases from fecal bacteria. In conclusion, the data show that following intravenous administration, (14) C-cilengitide was completely recovered, was excreted mainly via renal elimination, and was not metabolized systemically.
authors: Merck Serono-Global Early Development, Department of Clinical Pharmacology, Merck KGaA, Darmstadt, Germany.
authors: Andreas
authors: A
authors: Becker
authors: Merck Serono-Global Early Development, Department of Clinical Pharmacology, Merck KGaA, Darmstadt, Germany.
authors: Oliver
authors: O
authors: von Richter
authors: Sanofi Aventis, Frankfurt am Main, Germany.
authors: Andreas
authors: A
authors: Kovar
authors: Merck Serono-Global Early Development, Institute of Drug Metabolism and Pharmacokinetics, Merck KGaA, Grafing, Germany.
authors: Holger
authors: H
authors: Scheible
authors: Pharmaceutical Research Association (PRA), Zuidlaren, The Netherlands.
authors: Jan J
authors: JJ
authors: van Lier
authors: Merck Serono-Global Early Development, Department of Clinical Pharmacology, Merck KGaA, Darmstadt, Germany.
authors: Andreas
authors: A
authors: Johne
mesh_terms: D000328:Adult; D006801:Humans; D007262:Infusions, Intravenous; D039302:Integrin alphaVbeta3 / Q000037:antagonists & inhibitors*; D008297:Male; D019030:Receptors, Vitronectin / Q000037:antagonists & inhibitors*; D012910:Snake Venoms / Q000008:administration & dosage / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: D039302:Integrin alphaVbeta3; D019030:Receptors, Vitronectin; D012910:Snake Venoms; C064660:integrin alphaVbeta5; C422910:Cilengitide
keywords: cilengitide; disposition; human; mass balance