Modeling Whole-Body Dynamic PET Microdosing Data to Predict the Whole-Body Pharmacokinetics of Glyburide in Humans.
Léa Comin, Solène Marie, Moreno Ursino, Sarah Zohar, Nicolas Tournier, Emmanuelle Comets
Clinical Pharmacokinetics November 1, 2025 DOI: 10.1007/s40262-025-01562-9 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational cohort Peer reviewed |
|---|---|
| Sample size | 16 |
| Population | Healthy subjects |
| Intervention | Rifampicin |
| Duration | 40 min after injection |
| Topics | Microdosing |
| Key findings | A pharmacokinetic model built from whole-body dynamic PET microdose data for glyburide produced parameters consistent with standard blood-based pharmacokinetic studies, and rifampicin decreased liver distribution by 261%. |
Abstract
Whole-body dynamic (WB4D) positron emission tomography (PET) imaging data using radiolabeled analogs of drugs are mostly analyzed using descriptive approaches, with no relationship to traditional pharmacokinetic studies based on blood sampling. Here, we build a pharmacokinetic (PK) model from WB4D PET data obtained using a microdose of radiolabeled glyburide ([11C]glyburide) in humans, aiming to describe the biodistribution of this drug and compare estimated pharmacokinetic parameters with the parameters obtained in standard PK studies. The present work analyzes data acquired over 40 min after injection of [11C]glyburide in 16 healthy subjects using non-linear mixed-effect models (NLMEM). In 10 subjects, a second PET acquisition was performed after rifampicin administration, which may cause a drug-drug interaction and inhibit the liver uptake transport of glyburide. Arterial blood, liver, kidneys, pancreas, and spleen kinetics were modeled using NLMEM. The model-building strategy involved selecting the structural model using baseline [11C]glyburide PET data and then selecting the covariate model (rifampicin, age, and gender) and refining the structure of the interindividual variability model using both administration periods. Model selection was based on the corrected Bayesian information criterion and implemented in Monolix software. The final model included seven compartments, with two compartments each for the Liver and kidneys to account for within-tissue exchanges. Rifampicin decreased the Liver distribution by 261%. The estimated central volume of distribution (V = 3.6 L) and elimination rate (k = 0.8 h-1) were consistent with the known pharmacokinetics of glyburide, which is a promising first step in leveraging microdose data to study the WB4D biodistribution. EudraCT identifier no. 2017-001703-69.
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| Psilocybin microdosers demonstrate greater observed improvements in mood and mental health at one month relative to non-microdosing controls Psilocybin microdosers and non-microdosing comparators | 2022 | Naturalistic observational study | n = 1,133 |
| Nonlinear Pharmacokinetics of Oral Quinidine and Verapamil in Healthy Subjects: A Clinical Microdosing Study Healthy subjects | 2011 | Observational cohort |