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Antimicrobial Agents and Chemotherapy, February 1999, p. 381-384, Vol. 43, No. 2
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Pharmacokinetics of the Antiviral Agent beta -D-2',3'-Didehydro-2',3'-Dideoxy-5-Fluorocytidine in Rhesus Monkeys

Li Ma,1,2 Selwyn J. Hurwitz,1,2 Junxing Shi,1,2 Jeffrey J. McAtee,3 Dennis C. Liotta,3 Harold M. McClure,4 and Raymond F. Schinazi1,2,4,*

Department of Pediatrics1 and Chemistry3 and Yerkes Regional Primate Research Center,4 Emory University, and Georgia Research Center for AIDS and HIV Infections, Veterans Affairs Medical Center,2 Decatur, Georgia 30033

Received 6 April 1998/Returned for modification 23 August 1998/Accepted 31 October 1998

The values of the pharmacokinetic parameters of the nucleoside antiretroviral agent beta -D-2',3'-didehydro-2',3'-dideoxy-5-fluorocytidine (D-D4FC) in rhesus monkeys were determined with a two-compartment model after the administration of a single dose. The average values for the terminal half-life, renal clearance, and total systemic clearance for the intravenous administration route were 3.6 h and 0.31 and 0.43 liter · kg-1 · h-1, respectively. The oral bioavailability of D-D4FC averaged 41%. For the intravenous administration route, 76% of the compound was recovered intact in the urine within 8 h, indicating that D-D4FC was eliminated mainly by renal excretion. D-D4FC was detected in the cerebrospinal fluid (CSF) at similar concentrations after administration by both the intravenous and oral routes. D-D4FC levels in plasma and CSF were higher than the median effective concentration for human immunodeficiency virus type 1 in vitro.

* Corresponding author. Mailing address: Veterans Affairs Medical Center, Medical Research 151, 1670 Clairmont Rd., Decatur, GA 30033. Phone: (404) 728-7711. Fax: (404) 728-7726. E-mail: rschina{at}emory.edu.

Antimicrobial Agents and Chemotherapy, February 1999, p. 381-384, Vol. 43, No. 2
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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