ArticleThe AAPS journal2020
Incorporating Pharmacological Target-Mediated Drug Disposition (TMDD) in a Whole-Body Physiologically Based Pharmacokinetic (PBPK) Model of Linagliptin in Rat and Scale-up to Human.
Article in The AAPS journal, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 10 citations in OpenAlex.
- Binding Kinetics Can Explain Linear and Nonlinear Pharmacokinetics of Dipeptidyl Peptidase-IV Inhibitors Within a Single Target-Mediated Framework.Pharmaceutical research · 2026Article
- Optimization of Dosing Regimens for Plasminogen Activation Inhibitor BT-114143 Using a Small Molecule TMDD Population PK and PD Model in Healthy Subjects.European journal of drug metabolism and pharmacokinetics · 2026Article
- Cross-Species Extrapolation of Neonatal Fc Receptor (FcRn) Binding Affinity to Predict Monoclonal Antibody Pharmacokinetics in Humans Using Physiologically Based Pharmacokinetic Modeling (PBPK): Are We There Yet?ACS pharmacology & translational science · 2025Article
- Target-Mediated Drug Disposition (TMDD) Revisited: High Versus Low-Affinity Approximations of the TMDD Model.CPT: pharmacometrics & systems pharmacology · 2025Article
- A physiologically-based quantitative systems pharmacology model for mechanistic understanding of the response to alogliptin and its application in patients with renal impairment.Journal of pharmacokinetics and pharmacodynamics · 2025Article
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Linagliptin demonstrates substantial nonlinear pharmacokinetics due to its saturable binding to its pharmacological target dipeptidyl peptide 4 (DPP-4), a phenomenon known as target-mediated drug disposition (TMDD). In the current study, we established a novel whole-body physiologically-based pharmacokinetic (PBPK)-TMDD model for linagliptin. This comprehensive model contains plasma and 14 tissue compartments, among which TMDD binding process was incorporated in 9 of them, namely the plasma, kidney, liver, spleen, lung, skin, salivary gland, thymus, and reproductive organs. Our final model adequately captured the concentration-time profiles of linagliptin in both plasma and various tissues in both wildtype rats and DPP4-deficient rats following different doses. The association rate constant (k
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