ReviewJournal of clinical pharmacology2020
Concept of Pharmacologic Target-Mediated Drug Disposition in Large-Molecule and Small-Molecule Compounds.
Review in Journal of clinical pharmacology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
70 citing papers in PubMed.
- Safety, Tolerability, Pharmacokinetics, and Immunogenicity of a BTLA Agonist Antibody (Venanprubart) in Healthy Participants, Patients with Systemic Lupus Erythematosus, and Patients with Psoriasis: Results From Three Phase 1 Studies.Clinical pharmacology in drug development · 2026Trial
- Safety, Pharmacokinetics, and Immunogenicity of Astegolimab, an Anti-ST2 Monoclonal Antibody, in Randomized, Phase I Clinical Studies.Clinical and translational science · 2025Trial
- A Novel Step-Up Dosage Regimen for Enhancing the Benefit-to-Risk Ratio of Mosunetuzumab in Relapsed or Refractory Follicular Lymphoma.Clinical pharmacology and therapeutics · 2025Trial
- A randomized phase I study of the safety and pharmacokinetics of BI 1291583 in healthy Japanese male subjects.British journal of clinical pharmacology · 2025Trial
- Pharmacokinetics, Safety and Tolerability of Intravenous Lenzilumab, an Anti-GM-CSF Monoclonal Antibody Drug, in Healthy Korean Subjects.Drug design, development and therapy · 2025Trial
- Randomized, double-blind, phase 1a single-ascending dose and food effect studies assessing safety and pharmacokinetics of EC5026 in healthy volunteers.Clinical and translational science · 2024Trial
- A Target-Mediated Drug Disposition Model to Explain Nonlinear Pharmacokinetics of the 11β-Hydroxysteroid Dehydrogenase Type 1 Inhibitor SPI-62 in Healthy Adults.Journal of clinical pharmacology · 2021Trial
- Longitudinal Impact of Acute Spinal Cord Injury on Clinical Pharmacokinetics of Riluzole, a Potential Neuroprotective Agent.Journal of clinical pharmacology · 2021Trial
- Safety, pharmacokinetics and pharmacodynamics of BI 655064 in phase 1 clinical trials in healthy Chinese and Japanese subjects.British journal of clinical pharmacology · 2021Trial
- Clinical Impact of Target-Mediated Drug Disposition of Small Molecules with Focus on Early Phase I Study Designs.Clinical pharmacology and therapeutics · 2026Article
- Subcutaneous MG1113 in severe hemophilia A and B: phase 1b study for safety, pharmacokinetics, and pharmacodynamics.Research and practice in thrombosis and haemostasis · 2026Article
- Calculating Receptor Occupancy using TMDD Models - What has to be Considered?The AAPS journal · 2026Article
- PK and PK/PD Modeling of Bcl2 Inhibitor S65487 in Patients With AML and Investigation of Nonlinearity With Microdosing.CPT: pharmacometrics & systems pharmacology · 2026Article
- Biologics in Kidney Transplantation: Why and How Should We Personalize Their Dosage?BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026Review
- Rebinding drives cellular retention of small-molecule drugs with abundant targets.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Debio 1562M CD37-targeting ADC is highly active and well tolerated in preclinical models of AML and MDS.Cell reports. Medicine · 2026Article
- Safety, Tolerability, and Pharmacokinetics of 6-Diazo-5-Oxo-L-Norleucine in Malawian Adults With and Without Malaria: A Phase 1 Dose-Escalation Clinical Trial.The Journal of infectious diseases · 2026Article
- Candidozyma auris-infected Galleria mellonella larvae: the effect of the humanized monoclonal antibody Dia-T51 and its synergy with amphotericin B.npj antimicrobials and resistance · 2026Article
- Review
- 2-Methoxystypandrone fromAntioxidants (Basel, Switzerland) · 2026Article
10 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
1 author.
Funding
Abstract
Target-mediated drug disposition (TMDD) is a term to describe a nonlinear pharmacokinetic (PK) phenomenon that is caused by high-affinity binding of a compound to its pharmacologic targets. As the interaction between a drug and its pharmacologic target belongs to the process of pharmacodynamics (PD), TMDD can be viewed as a consequence of "PD affecting PK." Although there are numerous TMDD-related articles in the literature, most of them focus on characterizing TMDD using various mathematical models, which may not be suitable for those readers who have little interest in mathematical modeling and only want to have an understanding of the basic concept. The goal of this review is to serve as a "primer" on TMDD. This review explains (1) how TMDD happens; (2) why large-molecule and small-molecule compounds exhibiting TMDD demonstrate substantially different nonlinear PK behaviors; (3) what nonlinear PK profiles look like in large-molecule and small-molecule compounds exhibiting TMDD, using pegfilgrastim, erythropoietin, ABT-384, and linagliptin as case examples; and (4) how to identify whether the nonlinear PK of a compound is because of TMDD.
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Registered trials
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.