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Pharmacokinetics of the anticancer agent 2-chloro-9-(2-deoxy-2-fluoro-β-d-arabinofuranosyl)adenine in rats

  • Original Articles
  • Antimetabolites, 2′-Deoxyadenosine analogues, HPLC analysis, Chemotherapy, Pharmacokinetics
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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.

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Author notes

  1. Mingxin Qian & James M. Gallo

    Present address: Department of Medical Oncology, Fox Chase Cancer Center, 7701 Burholme Avenue, 19111, Philadelphia, PA, USA

  2. Xiaogen Wang

    Present address: Chongqing University of Medical Sciences, Chongqing, China

Authors and Affiliations

  1. Department of Pharmaceuties, College of Pharmacy, University of Georgia, Athens, Georgia, USA

    Mingxin Qian, Xiaogen Wang & James M. Gallo

  2. Department of Medicinal Chemistry, College of Pharmacy, University of Georiga, Athens, Georgia, USA

    Kirupa Shanmuganathan & Chung K. Chu

Authors
  1. Mingxin Qian
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  2. Xiaogen Wang
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  3. Kirupa Shanmuganathan
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  4. Chung K. Chu
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  5. James M. Gallo
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Qian, M., Wang, X., Shanmuganathan, K. et al. Pharmacokinetics of the anticancer agent 2-chloro-9-(2-deoxy-2-fluoro-β-d-arabinofuranosyl)adenine in rats. Cancer Chemother. Pharmacol. 33, 484–488 (1994). https://doi.org/10.1007/BF00686505

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  • DOI: https://doi.org/10.1007/BF00686505

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