ArticleClinical pharmacology and therapeutics2026
Mechanistic Population Pharmacokinetic Modeling of Extended-Release Metformin in Obese South African Women Living with HIV on Dolutegravir.
Article in Clinical pharmacology and therapeutics, 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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Abstract
Regulatory limits on metformin co-administered with dolutegravir (DTG) derive from healthy-volunteer studies in which DTG increased metformin exposure by 79% through organic cation transporter 2 inhibition, prompting a 1,000 mg/day metformin dose restriction. Whether this applies to women with HIV and severe obesity, a clinically important and understudied population for metformin-DTG coadministration, is unknown. In a secondary analysis of a reported cohort, we developed a population pharmacokinetic model of extended-release (XR) metformin with a zero-order-release, first-order-absorption structure scaled by lean body mass (LBM). Estimated glomerular filtration rate and DTG exposure were evaluated as clearance covariates, including DTG as a time-varying competitive inhibitor. We simulated steady-state exposures across body mass index (BMI) 30-60 kg/m
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