ArticleClinical pharmacokinetics2024
A Population Pharmacokinetic Study to Evaluate Doxorubicin Exposure Across All Age Groups.
Article in Clinical pharmacokinetics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Authors and funding
13 authors.
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Abstract
backgroundThe 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.
methodsA 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 (E
resultsA 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 E
conclusionA 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.
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