Evidence map›Paper›PMID 42814376›Full record

ArticleClinical pharmacokinetics2026

Understanding Pharmacokinetic Variability of Pomalidomide: A Physiologically Based Pharmacokinetic Analysis of Disease-Related Physiology, Ethnicity, Hepatic Impairment, Food Effects, Drug Interactions, and Smoking.

Jeffry Adiwidjaja, Alan V Boddy, Andrew J McLachlan

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Article in Clinical pharmacokinetics, 2026. 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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1 · What the graph read from it

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4 · The record

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5 · Who and what money

Authors and funding

3 authors.

Jeffry AdiwidjajaSydney Pharmacy School, The University of Sydney, Science Road, Camperdown Campus, Sydney, NSW, 2006, Australia. jeffry.adiwidjaja@sydney.edu.au.ORCID http://orcid.org/0000-0002-6781-2113
Alan V BoddySchool of Pharmacy and Biomedical Sciences, Adelaide University, Adelaide, SA, Australia.ORCID http://orcid.org/0000-0002-8920-9286
Andrew J McLachlanSydney Pharmacy School, The University of Sydney, Science Road, Camperdown Campus, Sydney, NSW, 2006, Australia.ORCID http://orcid.org/0000-0003-4674-0242

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND AND

objectiveUnderstanding interindividual pharmacokinetic variability and potential for drug interactions is of clinical importance for pomalidomide given its long-term use in patients with relapsed and/or refractory multiple myeloma (RRMM). This study aimed to develop a physiologically based pharmacokinetic (PBPK) model of pomalidomide that integrates multiple sources of pharmacokinetic (PK) variability, including RRMM-related physiology, ethnicity, hepatic impairment, food effects, drug interactions, and cigarette smoking.

methodsA PBPK model was developed incorporating in silico-predicted and experimentally measured physicochemical and biopharmaceutical properties, together with physiological parameters representing disease state, liver function, prandial status, and ethnic differences. Changes in PK and systemic exposure associated with multiple sources of variability, evaluated as shifts in central tendency, were predicted by the model.

resultsThe model provided reliable estimates of observed PK profiles across all evaluated scenarios, with more than 90% of predicted PK metrics falling within 0.80- to 1.25-fold of clinically reported values. Changes in pharmacokinetics associated with RRMM in people of European and Japanese ancestry, as well as severity-graded hepatic impairment, were reasonably predicted, despite slight overestimation of systemic exposure in severe hepatic impairment (prediction-to-reported ratio ≈ 1.55). Physiologically based pharmacokinetic model predictions of the effect of co-administration with high-fat, high-calorie meals (15-30% reduction in C

conclusionsOverall, this work highlights the utility of a PBPK modelling framework in providing mechanistic insights into multiple sources of pomalidomide PK variability, with potential broader applicability to other drugs.

Identifiers

PMID42814376

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