PBPK Modeling of Varenicline: Relating Variable Pharmacokinetics to Genomics.

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Article in European journal of drug metabolism and 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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2 authors.

Sanskruti SharmaDepartment of Pharmacology and Pharmaceutical Sciences, Alfred E. Mann School of Pharmacy and Pharmaceutical Sciences, University of Southern California, 1985 Zonal Avenue, Los Angeles, CA, 90089, USA.ORCID http://orcid.org/0009-0002-2043-1492

Ian S HaworthDepartment of Pharmacology and Pharmaceutical Sciences, Alfred E. Mann School of Pharmacy and Pharmaceutical Sciences, University of Southern California, 1985 Zonal Avenue, Los Angeles, CA, 90089, USA. ihaworth@usc.edu.ORCID http://orcid.org/0000-0002-3873-0899

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND AND

objectiveVarenicline is a smoking cessation drug that requires dosing over days to weeks to reach a pharmacologically effective concentration, since higher doses may result in nausea and vomiting. High interindividual variability in varenicline pharmacokinetics may also be related to these adverse effects. This study aimed to identify possible genetic causes of this variability using physiologically based pharmacokinetic (PBPK) modeling.

methodsA mean PBPK model of varenicline with mechanistic absorption, metabolism, and renal clearance was built using four patient populations. This model was then used to simulate pharmacokinetics in 20 individuals, adjusting SLC22A2 (OCT2) transporter kinetics and physiology to fit the simulations to the observed data.

resultsThe mean model included parameters for renal clearance through OCT2 (V

conclusionIndividuals with high varenicline exposure may have reduced renal elimination due to genetic variation in SLC22A2 (OCT2), while those with higher C

Identifiers

PMID42893471

DOI10.1016/j.apsb.2016.04.004

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.