Single-dose pharmacokinetics and metabolism of [14C]remofovir in rats and cynomolgus monkeys.

Abstract

Single-dose pharmacokinetics and metabolism of [(14)C]remofovir was studied in rats and monkeys following intravenous (i.v.) and oral administration (30 mg/kg of body weight). Oral absorption and bioavailability were 29.7 and 5.42% in rats and 65.6 and 19.4% in monkeys, respectively. Following i.v. administration, the elimination half-life for remofovir was 0.7 h in both rats and monkeys. Total body clearance was 5.85 liters/h/kg in rats and 2.60 liters/h/kg in monkeys; apparent volume of distribution was 5.99 liters/kg in rats and 2.70 liters/kg in monkeys. Following oral administration, remofovir was extensively converted to 9-(2-phosphonylmethoxyethyl)adenine (PMEA) and other metabolites in both species. In rats, excretion of total radioactivity in urine accounted for 61.8% of the i.v. dose and 12.9% of the oral dose, while in monkeys it accounted for 43.3% of the i.v. dose and 34.9% of the oral dose. Following i.v. dosing of [(14)C]remofovir, fecal excretion of radioactivity accounted for 37.5% of the dose in rats and 17.4% of the dose in monkeys, indicating significant biliary excretion of the drug in animals. PMEA and metabolite A were the major urinary metabolites in both species after i.v. and oral administration of remofovir.

• Authors: Chin-Chung Lin, Christine Xu, Nanqun Zhu, David Lourenco, Li-Tain Yeh
• Journal: Antimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 49 Issue 3 Pg. 925-30 (Mar 2005) ISSN: 0066-4804 [Print] United States
• PMID: 15728885 (Publication Type: Journal Article)

Chemical References

• Carbon Radioisotopes
• Organophosphorus Compounds
• Prodrugs
• pradefovir
• Adenine

Topics

• Adenine (analogs & derivatives, pharmacokinetics)
• Animals
• Area Under Curve
• Carbon Radioisotopes
• Half-Life
• Macaca fascicularis
• Male
• Organophosphorus Compounds (pharmacokinetics)
• Prodrugs
• Rats
• Rats, Sprague-Dawley
• Species Specificity