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

Publisher: Springer Verlag Country of Publication: Germany NLM ID: 7806519 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1432-0843 (Electronic) Linking ISSN: 03445704 NLM ISO Abbreviation: Cancer Chemother Pharmacol Subsets: MEDLINE

Publication: Berlin : Springer Verlag
Original Publication: Berlin, New York, Springer International.

Antimetabolites, Antineoplastic* ; Deoxycytidine*/analogs & derivatives; Aged ; Humans ; Infusions, Intravenous ; Research Design ; Gemcitabine

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.
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.
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.
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.
Trial Registration Number: NL39647.048.12, registered on May 3rd 2012.
(© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

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Keywords: 2′,2′-Difluorodeoxyuridine; Age; Gemcitabine; Pharmacokinetics; Precision dosing

NTR NL39647.048.12

0 (Antimetabolites, Antineoplastic)
0W860991D6 (Deoxycytidine)
0 (Gemcitabine)

Date Created: 20220415 Date Completed: 20220503 Latest Revision: 20221207

20240829

10.1007/s00280-022-04431-5

35426526