Drug Concentration Asymmetry in Tissues and Plasma for Small Molecule-Related Therapeutic Modalities

• Published in: Drug metabolism and disposition Vol. 47; no. 10; pp. 1122 - 1135
• Main Authors: Zhang, Donglu, Hop, Cornelis E C A, Patilea-Vrana, Gabriela, Gampa, Gautham, Seneviratne, Herana Kamal, Unadkat, Jashvant D, Kenny, Jane R, Nagapudi, Karthik, Di, Li, Zhou, Lian, Zak, Mark, Wright, Matthew R, Bumpus, Namandjé N, Zang, Richard, Liu, Xingrong, Lai, Yurong, Khojasteh, S Cyrus
• Format: Journal Article
• Language: English
• Published: United States American Society for Pharmacology and Experimental Therapeutics, Inc 01.10.2019; The American Society for Pharmacology and Experimental Therapeutics
• Subjects: Animals; Antibodies; Asymmetry; Binders; Biotransformation; Cell Membrane - metabolism; Chemical compounds; Drug delivery; Drug delivery systems; Drug development; Drug Discovery - methods; Drugs; Efflux; Extrusion; Forecasting; Humans; Immunoconjugates - pharmacokinetics; Inhalation; Membrane Transport Proteins - metabolism; Minireview; Nanoparticles; Optimization; Pharmacodynamics; Pharmacokinetics; Pharmacology; Plasma; Plasma - metabolism; Prodrugs; Prodrugs - pharmacokinetics; Respiration; Steady state; Therapeutic applications; Tissue Distribution; Tissues

The well accepted "free drug hypothesis" for small-molecule drugs assumes that only the free (unbound) drug concentration at the therapeutic target can elicit a pharmacologic effect. Unbound (free) drug concentrations in plasma are readily measurable and are often used as surrogates for th...