Is age just a number? A population pharmacokinetic study of gemcitabine.

Abstract

METHODS

Pharmacokinetic sampling following a flexible limited sampling strategy was performed in patients ≥ 70 years after gemcitabine infusion. The data were supplemented with pharmacokinetic data in patients included in four previously conducted clinical trials. Nonlinear mixed effects modelling was performed on the pooled dataset to assess the impact of age on the pharmacokinetics of gemcitabine and dFdU.

PURPOSE

Pharmacokinetic exposure to gemcitabine and its metabolite, 2',2'-difluorodeoxyuridine (dFdU), might be altered in elderly compared to their younger counterparts. It is unknown if age-based dose adjustments are necessary to reduce the development of treatment-induced adverse events. The aim of this study was to assess the impact of age on the pharmacokinetics of gemcitabine and dFdU.

CONCLUSION

Age was not of influence on the pharmacokinetics of gemcitabine or its metabolite, dFdU. Age-related dose adjustments for gemcitabine based on pharmacokinetic considerations are not recommended.

RESULTS

In total, pharmacokinetic data were available of 197 patients, of whom 83 patients were aged ≥ 70 years (42%). A two-compartment model for both gemcitabine and dFdU with linear clearances from the central compartments described the data best. Age, tested as continuous and categorical (< 70 years versus ≥ 70 years) covariate, did not statistically affect the pharmacokinetics of gemcitabine and dFdU.

TRIAL REGISTRATION NUMBER

NL39647.048.12, registered on May 3rd 2012.

More about this publication

Cancer chemotherapy and pharmacology
  • Volume 89
  • Issue nr. 5
  • Pages 697-705
  • Publication date 01-05-2022

This site uses cookies

This website uses cookies to ensure you get the best experience on our website.