Single Dose Pharmacokinetics and Bioavailability Study of Dideoxyadenosine (NSC-98700) in Beagle Dogs

摘要

The study, I.V. doses of ddA appeared to be rapidly deaminated to ddI. The kinetics of ddA were dose-dependent, with a half-life (based on ddI clearance) of approximately 61 minutes following a ddA dose of 500 mg/kg and 24 minutes following a ddA dose of 100 mg/kg. This suggests there is concentration-limited metabolism of ddI, resulting in disproportionate increases in plasma ddI levels with increased ddA doses. Oral doses of ddA were poorly tolerated and only partially retained and absorbed. The partial loss of oral doses due to emesis shortly after dosing complicated the determination of the bioavailability of orally administered ddA.