ArticleClinical and translational science2024
Elucidation of DPP-4 involvement in systemic distribution and renal reabsorption of linagliptin by PBPK modeling with a cluster Gauss-Newton method.
Article in Clinical and translational science, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Binding Kinetics Can Explain Linear and Nonlinear Pharmacokinetics of Dipeptidyl Peptidase-IV Inhibitors Within a Single Target-Mediated Framework.Pharmaceutical research · 2026Article
- Characterizing Apixaban Pharmacokinetics Through Physiologically-Based Pharmacokinetic Modeling: Critical Role of Biliary Secretion and Enterohepatic Circulation in Humans.CPT: pharmacometrics & systems pharmacology · 2026Article
- Simultaneous Target-Mediated Drug Disposition-Pharmacodynamic (TMDD-PD) Modeling of Finasteride and Dutasteride: Impact of Target Binding and Turnover on Non-linear Pharmacokinetics.The AAPS journal · 2025Article
- Elucidation of DPP-4 involvement in systemic distribution and renal reabsorption of linagliptin by PBPK modeling with a cluster Gauss-Newton method.Clinical and translational science · 2024Article
Corrections and comments
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Authors and funding
5 authors.
Funding
Abstract
The dipeptidyl peptidase-4 (DPP-4) inhibitor linagliptin (LNG) exhibits target-mediated drug disposition (TMDD) in clinical settings, characterized by saturable binding to plasma soluble DPP-4 (sDPP-4) and tissue transmembrane DPP-4 (tDPP-4). Previous studies have indicated that saturable renal reabsorption of LNG contributes to its nonlinear urinary excretion observed in humans and wild-type mice, but not in Dpp-4 knockout mice. To elucidate the mechanisms underlying these complex phenomena, including DPP-4-related renal reabsorption of LNG, we employed physiologically-based pharmacokinetic (PBPK) modeling combined with a cluster Gauss-Newton method (CGNM). The CGNM facilitated the exploration of parameters in rat and human PBPK models for LNG and the determination of parameter identifiability. Through PBPK-CGNM analysis using reported autoradiography data ([
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