ArticlePharmaceutical research2022
Free Drug Theory - No Longer Just a Hypothesis?
Article in Pharmaceutical research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed.
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- Complex Distribution Phenomena and Plastic Binding of Test Chemicals in Cell Culture Experiments: Exemplification by Tebufenpyrad.International journal of molecular sciences · 2026Article
- Accounting for Differences in Plasma Protein Binding between Fish and Humans for Supporting Environmental Risk Assessment of Pharmaceuticals Using the Fish Plasma Model.Environmental science & technology · 2026Article
- Preclinical efficacy of the muscarinic agonist ML-007 in psychosis models depends on both MNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Tumor-Targeted Delivery of an EGFR Inhibitor Prodrug via Site-Specific Albumin Conjugation.Journal of medicinal chemistry · 2026Article
- Glioma drug development benefits from emerging phase 0 and window-of-opportunity trial paradigm.Cell communication and signaling : CCS · 2025Review
- One-step Immobilization of Human α-1-acid Glycoprotein on Magnetic Beads: A Rapid Method for Small Molecule hAGP Binding Study.The AAPS journal · 2025Article
- Concentration-dependent blood binding: assessing implications through physiologically based Pharmacokinetic modeling of tacrolimus as a case example.Journal of pharmacokinetics and pharmacodynamics · 2025Article
- Discovery of Cell-Permeable Macrocyclic Cyclin A/B RxL Inhibitors that Demonstrate Antitumor Activity.Journal of medicinal chemistry · 2025Article
- The Pharmacokinetic and Pharmacodynamic Relationship of Clinically Used Antiseizure Medications in the Maximal Electroshock Seizure Model in Rodents.International journal of molecular sciences · 2025Article
- Toxicokinetics and Perfluorooctanesulfonic Acid-Induced Liver Protein Expression Are Markedly Altered in Mice Lacking Albumin.Chemical research in toxicology · 2025Article
- Understanding Mechanisms of PFAS Absorption, Distribution, and Elimination Using a Physiologically Based Toxicokinetic Model.Environmental science & technology · 2025Article
- Discovery of orally bioavailable Zika and West Nile Virus antiviral compounds targeting the NS2B-NS3 protease.bioRxiv : the preprint server for biology · 2025Article
- Deciphering the Tumor Uptake of Heterobivalent (SSTJournal of medicinal chemistry · 2025Article
- Thalidomide-induced limb malformations: an update and reevaluation.Archives of toxicology · 2025Review
- Beyond-Rule-of-Five Compounds Are Not Different: In Vitro-In Vivo Extrapolation of Female CD-1 Mouse Clearance Based on Merck Healthcare KGaA Compound Set.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Mass spectrometry methods and mathematical PK/PD model for decision tree-guided covalent drug development.Nature communications · 2025Article
- A Sequential Ultrafiltration Method to Enhance the Accuracy and Throughput in Plasma Protein Binding Tests.Pharmaceutics · 2025Article
- Novel Cyclohexyl Amido Acid Antagonists of Lysophosphatidic Acid Type 1 Receptor for the Treatment of Pulmonary Fibrosis.ACS medicinal chemistry letters · 2025Article
Corrections and comments
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Authors and funding
3 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Free Drug Hypothesis is a well-established concept within the scientific lexicon pervading many areas of Drug Discovery and Development, and yet it is poorly defined by virtue of many variations appearing in the literature. Clearly, unbound drug is in dynamic equilibrium with respect to absorption, distribution, metabolism, elimination, and indeed, interaction with the desired pharmacological target. Binding interactions be they specific (e.g. high affinity) or nonspecific (e.g. lower affinity/higher capacity) are governed by the same fundamental physicochemical tenets including Hill-Langmuir Isotherms, the Law of Mass Action and Drug Receptor Theory. With this in mind, it is time to recognise a more coherent version and consider it the Free Drug Theory and a hypothesis no longer. Today, we have the experimental and modelling capabilities, pharmacological knowledge, and an improved understanding of unbound drug distribution (e.g. Kp
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