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Antimicrobial Agents and Chemotherapy, March 2005, p. 925-930, Vol. 49, No. 3
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.3.925-930.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Single-Dose Pharmacokinetics and Metabolism of [14C]Remofovir in Rats and Cynomolgus Monkeys

Chin-Chung Lin,1* Christine Xu,1 Nanqun Zhu,1 David Lourenco,1 and Li-Tain Yeh1

Research and Development, Valeant Pharmaceuticals International, Costa Mesa, California1

Received 9 August 2004/ Returned for modification 7 October 2004/ Accepted 11 November 2004

Single-dose pharmacokinetics and metabolism of [14C]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 [14C]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.

* Corresponding author. Mailing address: Valeant Pharmaceuticals International, 3300 Hyland Ave., Costa Mesa, CA 92626. Phone: (714) 427-6236, ext. 2062. Fax: (714) 641-7201. E-mail: cclin{at}valeant.com.

Antimicrobial Agents and Chemotherapy, March 2005, p. 925-930, Vol. 49, No. 3
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.3.925-930.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Lin, C.-c., Fang, C., Benetton, S., Xu, G.-f., Yeh, L.-T. (2006). Metabolic Activation of Pradefovir by CYP3A4 and Its Potential as an Inhibitor or Inducer.. Antimicrob. Agents Chemother. 50: 2926-2931 [Abstract] [Full Text]  


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