Absorption, pharmacokinetics and excretion of levovirin in rats, dogs and cynomolgus monkeys.
The absorption, pharmacokinetics and excretion of levovirin were studied in Sprague-Dawley rats (30 mg/kg) and Beagle dogs (30 mg/kg) following intravenous (iv) and oral administration of [(3)H]levovirin, and in Cynomolgus monkeys following iv and oral administration of [(14)C]levovirin. Oral absorption was 31.3% in rats, 67.3% in dogs and 17.5% in monkeys, and the bioavailability was 29.3% in rats, 51.3% in dogs and 18.4% in monkeys. After iv administration, the elimination half-life (t(1/2)) was 1.47 h in rats, 3.70 h in dogs and 3.50 h in monkeys. The total body clearance was 8.24, 2.96 and 2.58 mL/min per kg, respectively, in rats, dogs and monkeys and the apparent volume of distribution was 0.79, 0.95 and 0.65 L/kg. No metabolite was detected in plasma or urine of rats, dogs or monkeys, indicating negligible metabolism of levovirin in these animals. Excretion of total radioactivity in urine after oral dosing accounted for 15.4% of the administered dose in rats, 49.9% in dogs and 21.4% in monkeys. Biliary excretion did not play a significant role in the elimination of levovirin.
Lin
Chin-Chung
CC
Research and Development, Ribapharm, Inc, 3300 Hyland Avenue, Costa Mesa, CA 92626, USA. cclin@ribapharm.com
Luu
Trong
T
Lourenco
David
D
Yeh
Li-Tain
LT
Lau
Johnson Y N
JY
D000042:Absorption / Q000187:drug effects / Q000502:physiology; D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D004285:Dogs; D005243:Feces / Q000737:chemistry; D007275:Injections, Intravenous; D008252:Macaca fascicularis; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012254:Ribavirin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine*; D013237:Stereoisomerism
D012254:Ribavirin