ISSN:
1432-0843
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract The pharmacokinetics of a new 2-halo-2′-deoxyadenosine analogue, 2-chloro-9-(2-deoxy-2-fluoro-β-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 biovailability estimates of approximately 50%, indicating that oral treatment regimens of CL-F-ara-A are feasible.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00686505
