Pharmacokinetics and metabolism of [14C]viramidine in rats and cynomolgus monkeys.
The pharmacokinetics of [(14)C]viramidine, a prodrug of ribavirin, were studied in rats (30 mg/kg of body weight) and monkeys (10 mg/kg) following intravenous (i.v.) and oral administration. The levels of oral absorption and bioavailabilities were 61.7 and 9.91%, respectively, in rats and 43.9 and 13.6%, respectively, in monkeys. Following i.v. administration, the elimination half-lives were 2.7 h in rats and 28.9 h in monkeys. Total body clearances were 14.0 liters/h/kg in rats and 1.23 liters/h/kg in monkeys; the apparent volumes of distribution were 15.6 liters/kg in rats and 18.6 liters/kg in monkeys. Following oral administration, viramidine was extensively converted to ribavirin, followed by further metabolism of ribavirin in both species, with a faster rate of metabolism in rats than in monkeys. In rats, excretion of total radioactivity in urine accounted for 77.0% of the i.v. dose and 60.8% of the oral dose, while in monkeys it accounted for 44.4% of the i.v. dose and 39.0% of the oral dose. The amount of unchanged viramidine and ribavirin in urine was small in both species after i.v. and oral administration of viramidine.
Lin
Chin-Chung
CC
Research and Development, Ribapharm, Inc., Costa Mesa, California 92626, USA. cclin@ribapharm.com
Luu
Kenneth
K
Lourenco
David
D
Yeh
Li-Tain
LT
D000284:Administration, Oral; D000818:Animals; D000998:Antiviral Agents / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D005243:Feces / Q000737:chemistry; D006207:Half-Life; D007275:Injections, Intravenous; D007408:Intestinal Absorption; D008252:Macaca fascicularis; D008297:Male; D013058:Mass Spectrometry; D011355:Prodrugs / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012254:Ribavirin / Q000031:analogs & derivatives / Q000493:pharmacokinetics*; D013045:Species Specificity
D000998:Antiviral Agents; D011355:Prodrugs; D012254:Ribavirin; C026956:taribavirin