Application of population pharmacokinetics to cladribine

BMC Pharmacol. 2005 Mar 9:5:4. doi: 10.1186/1471-2210-5-4.


Background: The nucleoside analog cladribine is used for the treatment of a variety of indolent B- and T-cell lymphoid malignancies. The primary aim of the study was to evaluate the population distribution of pharmacokinetic parameters in patients undergoing treatment with cladribine and to detect the influence of different covariates on the pharmacokinetic parameters.

Methods: This pharmacokinetic study presents the results of a retrospective population pharmacokinetic analysis based on pooled data from 161 patients, who were given cladribine in different administration routes in various dosing regimens. The plasma concentrations of cladribine were determined by reversed-phase high-performance liquid chromatography using a solid phase extraction with a limit of quantitation of 1 nM using 1 mL of plasma.

Results: A three compartment structural model best described the disposition of cladribine. Clearance was found to be 39.3 L/hour, with a large interindividual variability. The half-life for the terminal phase was 16 hours. Bioavailability was 100% and 35% for subcutaneous and oral administration, respectively, with low interindividual variability. None of the investigated covariates were found to be correlated with the pharmacokinetic parameters.

Conclusion: As interindividual variability in apparent clearance after oral administration was not significantly higher compared to that following infusion, cladribine could be administered orally instead of intravenously if compensated for its lower bioavailability. Individualized dosing on basis of body surface area or weight does not represent an improvement in this study as compared to administering a fixed dose to all patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / blood
  • Antineoplastic Agents / pharmacokinetics*
  • Area Under Curve
  • Biological Availability
  • Cladribine / administration & dosage
  • Cladribine / blood
  • Cladribine / pharmacokinetics*
  • Female
  • Humans
  • Infusions, Intravenous
  • Intestinal Absorption
  • Male
  • Metabolic Clearance Rate
  • Middle Aged
  • Multicenter Studies as Topic
  • Retrospective Studies


  • Antineoplastic Agents
  • Cladribine