Metabolism and disposition of the αv-integrin ß3/ß5 receptor antagonist cilengitide, a cyclic polypeptide, in humans
| العنوان: | Metabolism and disposition of the αv-integrin ß3/ß5 receptor antagonist cilengitide, a cyclic polypeptide, in humans |
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| المؤلفون: | Andreas Johne, Andreas Becker, Holger Scheible, Jan J. van Lier, Andreas Kovar, Oliver von Richter |
| المصدر: | The Journal of Clinical Pharmacology. 55:815-824 |
| بيانات النشر: | Wiley, 2015. |
| سنة النشر: | 2015 |
| مصطلحات موضوعية: | Adult, Male, medicine.medical_specialty, medicine.drug_class, Cilengitide, Urine, Pharmacology, Excretion, Young Adult, chemistry.chemical_compound, Pharmacokinetics, Internal medicine, medicine, Humans, Receptors, Vitronectin, Pharmacology (medical), Infusions, Intravenous, Feces, Metabolism, Integrin alphaVbeta3, Receptor antagonist, Endocrinology, Renal Elimination, chemistry, Snake Venoms |
| الوصف: | 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. |
| تدمد: | 0091-2700 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2b9b895fe0c66d19c914eb456439b19a https://doi.org/10.1002/jcph.482 |
| حقوق: | CLOSED |
| رقم الأكسشن: | edsair.doi.dedup.....2b9b895fe0c66d19c914eb456439b19a |
| قاعدة البيانات: | OpenAIRE |
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