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Clinical and Epidemiological Investigations

On the Pharmacokinetics of 2-Chloro-2′-deoxyadenosine in Humans

Jan Liliemark and Gunnar Juliusson
Jan Liliemark
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Gunnar Juliusson
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DOI:  Published October 1991
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Abstract

The antitumoral effect of 2-chloro-2′-deoxyadenosine (CdA) in the treatment of lymphoproliferative diseases in general and of hairy cell leukemia in particular has recently been demonstrated. Detailed information on the pharmacokinetics of CdA, however, is lacking. The pharmacokinetics of CdA after 2- and 24-h infusions of 0.14 mg/kg was described in 12 patients with lymphoproliferative diseases using a newly developed high-performance liquid chromatography method. The plasma concentration data from individual patients were fitted to a two-compartment model with α- and β-half-lives of 35 ± 12 (mean ± SD) min and 6.7 ± 2.5 h, respectively. The volume of distribution was 9.2 ± 5.4 liters/kg. The steady-state concentration of CdA during the 24-h infusion was 22.5 ± 11.1 nm. The areas under the time versus concentration curves were 552 ± 258 and 588 ± 185 nm × h, respectively, for the 24- and 2-h infusions. The interindividual variability of the determinants of the plasma pharmacokinetics of CdA was small (the coefficients of variation were between 0.22 and 0.58). At 6.3 ± 1.5 h after the start of the 2-h infusion, the concentration of CdA was the same as the steady-state concentration during the 24-h infusion. When the mean plasma concentrations of the 12 patients were fitted to a 3-compartment model, the half-lives of the α-, β-, and τ-phases were 8 min, 1 h 6 min, and 6.3 h, respectively. The long terminal half-life of CdA after 2-h infusion supports the use of intermittent infusions.

Footnotes

  • ↵1 Supported by grants from the Medical Research Council (Project 08460).

  • ↵2 To whom requests for reprints should be addressed.

  • Received April 9, 1991.
  • Accepted August 7, 1991.
  • ©1991 American Association for Cancer Research.
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October 1991
Volume 51, Issue 20
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On the Pharmacokinetics of 2-Chloro-2′-deoxyadenosine in Humans
Jan Liliemark and Gunnar Juliusson
Cancer Res October 15 1991 (51) (20) 5570-5572;

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On the Pharmacokinetics of 2-Chloro-2′-deoxyadenosine in Humans
Jan Liliemark and Gunnar Juliusson
Cancer Res October 15 1991 (51) (20) 5570-5572;
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