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  • Title: Disposition in animals of a new anti-HIV agent: 2',3'-didehydro-3'-deoxythymidine.
    Author: Russell JW, Whiterock VJ, Marrero D, Klunk LJ.
    Journal: Drug Metab Dispos; 1990; 18(2):153-7. PubMed ID: 1971565.
    Abstract:
    The pharmacokinetics and CNS penetration of the anti-human immunodeficiency virus agent 2',3'-didehydro-3'-deoxythymidine have been examined in CD-1 mice. The drug was rapidly cleared from plasma with a terminal half-life of 17 min after an iv bolus dose at 25 mg/kg. Oral absorption of 2',3'-didehydro-3'-deoxythymidine was rapid and complete (98% bioavailable) with plasma levels approximately the same as those measured after iv administration. Estimates of the total body clearance and apparent volume of distribution were 43 ml/hr and 19 ml, respectively. In the mouse, entry into the central nervous system was rapid but the concentrations were somewhat low. However, drug concentrations which were reported to be effective in inhibiting replication of the virus in cell culture, greater than 0.01 microM, could be measured in the brain after a single oral dose at 25 mg/kg. A study to examine the urinary excretion of the drug in CD rats, beagle dogs and cynomolgus monkeys showed that 2',3'-didehydro-3'-deoxythymidine was primarily renally excreted unchanged.
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