caa a22 4500 465812201 CHVBK 20180323112119.0 cr unu---uuuuu 170327e19900101xx s 000 0 eng 10.1007/BF03190126 doi (NATIONALLICENCE)springer-10.1007/BF03190126 Metabolic disposition and pharmacokinetics of pelrinone, a new cardiotonic drug, in laboratory animals and man [Elektronische Daten] [J. Scattna, D. Hicks, M. Kraml, M. Cayen] Summary: The metabolic disposition of pelrinone, a cardiotonic drug, was studied in mouse, rat, rabbit, dog, monkey and man. Pelrinone was rapidly and extensively absorbed in rodents, dogs, monkeys and man. Except in rabbits, the major portion of the serum radioactivity was due to parent drug. Pelrinone was moderately bound to human serum proteins and weakly bound to serum proteins from animals. Radioactive compounds were rapidly eliminated from rat tissues with the highest concentrations found in organs associated with absorption and elimination. After a 1.0 mg/kg i.v. dose, the rapid elimination of pelrinone from mouse, rat and dog serum precluded estimation of an elimination half life (t1/2). However, after higher oral or i.V. doses, a more prolonged elimination phase was apparent and the t1/2 of pelrinone ranged from 8-10 h in rodents and dogs. In human subjects given escalating oral or i.v. doses of pelrinone, the elimination t1/2 was independent of dose and averaged 1-2 h. The serum AUC of pelrinone was linearly dose-related following oral doses up to 20 mg/kg in dogs and 100 mg in man. In mice, a greater proportional increase in AUC occurred between oral doses of 2-100 mg/kg while in rats, the serum AUC increased in less than proportional manner from 10-200 mg/kg p.o. In ell species, radioactive compounds were excreted mainly in the urine. No metabolites were detected in dog and human urine while small amounts of unconjugated metabolites were excreted in mouse and rat urine. Springer-Verlag, 1990 Pelrinone nationallicence cardiotonic nationallicence pharmacokinetics nationallicence metabolic disposition nationallicence Scattna J. Drug Metabolism Division, Wyeth-Ayerst Research, CN 8000, 08543-8000, Princeton, New Jersey, USA aut Hicks D. Drug Metabolism Division, Wyeth-Ayerst Research, CN 8000, 08543-8000, Princeton, New Jersey, USA aut Kraml M. Drug Metabolism Division, Wyeth-Ayerst Research, CN 8000, 08543-8000, Princeton, New Jersey, USA aut Cayen M. Drug Metabolism Division, Wyeth-Ayerst Research, CN 8000, 08543-8000, Princeton, New Jersey, USA aut European Journal of Drug Metabolism and Pharmacokinetics Springer-Verlag 15/1(1990-01-01), 37-48 0378-7966 15:1<37 1990 15 13318 https://doi.org/10.1007/BF03190126 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF03190126 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Scattna J. Drug Metabolism Division, Wyeth-Ayerst Research, CN 8000, 08543-8000, Princeton, New Jersey, USA aut NATIONALLICENCE 700 1- Hicks D. Drug Metabolism Division, Wyeth-Ayerst Research, CN 8000, 08543-8000, Princeton, New Jersey, USA aut NATIONALLICENCE 700 1- Kraml M. Drug Metabolism Division, Wyeth-Ayerst Research, CN 8000, 08543-8000, Princeton, New Jersey, USA aut NATIONALLICENCE 700 1- Cayen M. Drug Metabolism Division, Wyeth-Ayerst Research, CN 8000, 08543-8000, Princeton, New Jersey, USA aut NATIONALLICENCE 773 0- European Journal of Drug Metabolism and Pharmacokinetics Springer-Verlag 15/1(1990-01-01), 37-48 0378-7966 15:1<37 1990 15 13318 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer