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Lookup NU author(s): Dr Shelby BarnettORCiD, Professor Gareth Veal
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© The Author(s), under exclusive licence to Springer Nature Switzerland AG 2024.Background: The effect of age on doxorubicin pharmacokinetics remains inconclusive, especially in patients at the extremes of the age spectrum. We developed a population pharmacokinetic model to further investigate the impact of age on the pharmacokinetics of doxorubicin. Methods: A three-compartment model, incorporating allometric scaling was developed to describe doxorubicin pharmacokinetics across all ages. First, the effect of age in young patients was investigated, by adding a maturation function on clearance (CL), the central compartment (V1) and peripheral compartments (V2 and V3). Second, the impact of ageing was investigated by adding a maximal effect (Emax) function on CL, V1, V2, and V3. To investigate the overall impact of age on doxorubicin exposure, various simulations were conducted. Results: A total of 168 patients (age: 0.11–90 years) with 555 doxorubicin samples were included. The maturation function was relevant for V1 and V2 (13.1 and 23.7 L, respectively), leading to an increase in V1 and V2 with increasing age. In contrast, adding an Emax function only impacted V3 (1063L), resulting in a decrease of V3 with age. Simulations showed no clinically relevant difference in the exposure of doxorubicin between age groups. Conclusion: A population pharmacokinetic model with data across the age range showed that age predominantly affected volumes of distribution of the central and peripheral compartments. These effects were not considered to be clinically relevant based on performed simulations. This supports the use of currently used doxorubicin dosages of 1 mg/kg for infants and toddlers < 10 kg and body surface area-based dosing for other patients.
Author(s): Mohmaed Ali MI, Nijstad AL, Boosman RJ, Crombag M-RBS, Barnett S, Veal GJ, Lalmohamed A, van Erp NP, Steeghs N, Zwaan CM, Beijnen JH, Siebinga H, Huitema ADR
Publication type: Article
Publication status: Published
Journal: Clinical Pharmacokinetics
Year: 2024
Pages: epub ahead of print
Online publication date: 16/11/2024
Acceptance date: 23/10/2024
ISSN (print): 0312-5963
ISSN (electronic): 1179-1926
Publisher: Springer
URL: https://doi.org/10.1007/s40262-024-01445-5
DOI: 10.1007/s40262-024-01445-5
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