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Pharmacokinetics of the anticancer agent 2-chloro-9-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)adenine in rats.

Author(s): Qian M, Wang X, Shanmuganathan K, Chu CK, Gallo JM

Affiliation(s): Department of Pharmaceuties, College of Pharmacy, University of Georgia, Athens.

Publication date & source: 1994, Cancer Chemother Pharmacol., 33(6):484-8.

The pharmacokinetics of a new 2-halo-2'-deoxyadenosine analogue, 2-chloro-9-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl) adenine [CL-F-ara-A], was characterized in rats following the development of a new high-performance liquid chromatography (HPLC) technique. This halogenated derivative was thought to have improved gastrointestinal stability that would facilitate oral administration. The HPLC method consisted of a single ethyl acetate extraction and reverse-phase chromatographic conditions. The method resulted in approximately 83% recovery of CL-F-ara-A from plasma and a sensitivity of 20 ng/ml. At i.v. doses of 10 and 25 mg/kg, the total clearance of CL-F-ara-A decreased from 2.1 to 1.5 l h-1 kg-1, with the reduction being attributed to saturation of metabolism. The elimination half-lives following i.v. bolus administrations were estimated to be a mean of 1.35 and 1.84 h at the two respective doses. The volume of distribution at steady state was not significantly different at the two doses, being 3.6 and 3.2 l/kg. The percentage of protein binding of CL-F-ara-A in rat plasma was only 13.3%. Administration of equivalent oral doses resulted in bioavailability estimates of approximately 50%, indicating that oral treatment regimens of CL-F-ara-A are feasible.

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