Document 0120
 DOCN  M9460120
 TI    Pharmacokinetics of 2',3'-dideoxy-5-fluoro-3'-thiacytidine in rats.
 DT    9404
 AU    Abobo CV; Ni L; Schinazi RF; Liotta DC; Boudinot FD; Department of
       Pharmacy Practice, College of Pharmacy and Health; Sciences, Texas
       Southern University, Houston 77004.
 SO    J Pharm Sci. 1994 Jan;83(1):96-9. Unique Identifier : AIDSLINE
       MED/94186956
 AB    Although several drugs have shown clinical anti-human immunodeficiency
       virus activity, reduced activity with long-term use and toxicity make
       new agents with high therapeutic indices desirable. Racemic
       cis-2',3'-dideoxy-5-fluoro-3'-thiacytidine (FTC) is a new synthetic
       nucleoside analogue that is usually potent against human
       immunodeficiency virus types 1 and 2 and hepatitis B virus in vitro. The
       purpose of this study was to characterize the preclinical
       pharmacokinetics of FTC in rats. Rats were administered 10, 50, and 100
       mg of FTC per kg of body weight intravenously. Concentrations of FTC in
       plasma and urine were determined by HPLC. Pharmacokinetic parameters
       were generated by area/moment analysis. Plasma FTC concentrations
       declined rapidly in a biexponential fashion, with a terminal half-life
       of approximately 2 h. The area under the plasma FTC concentration-time
       curve increased proportionally with increasing dose, and there were no
       statistically significant differences in pharmacokinetic parameters
       among the three doses. Thus, the disposition of FTC was independent of
       dose over the range of 10-100 mg/kg. Since the disposition of FTC was
       linear, pharmacokinetic parameters were averaged for the three doses.
       The average total clearance of FTC was 1.91 +/- 0.32 L/h/kg (mean +/-
       SD), the average renal clearance was 1.08 +/- 0.26 L/h/kg, and the
       average nonrenal clearance was 0.83 +/- 0.27 L/h/kg. Approximately 55%
       of the dose of FTC was recovered as unchanged drug in the urine. The
       steady-state volume of distribution of FTC averaged 2.17 +/- 0.59 L/kg.
 DE    Animal  Antiviral Agents/*PHARMACOKINETICS  Dose-Response Relationship,
       Drug  Male  Metabolic Clearance Rate  Rats  Rats, Sprague-Dawley
       Support, U.S. Gov't, Non-P.H.S.  Support, U.S. Gov't, P.H.S.
       Zalcitabine/*ANALOGS & DERIVATIVES/PHARMACOKINETICS  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).