Navigating Transporter Sciences in Pharmacokinetics Characterization Using the Extended Clearance Classification System.

摘要: Membrane transporters play an important role in the absorption, distribution, clearance, and elimination of drugs. Supported by pharmacokinetics data human, several including organic anion transporting polypeptide (OATP)1B1, OATP1B3, transporter (OAT)1, OAT3, cation (OCT)2, multidrug toxin extrusion (MATE) proteins, P-glycoprotein breast cancer resistance protein are suggested to be clinical relevance. An early understanding drug disposition clearance allows reliable prediction/evaluation changes due drug-drug interactions (DDIs) or genetic polymorphisms. We recently proposed extended classification system (ECCS) based on simple properties (i.e., ionization, permeability, molecular weight) predict predominant mechanism. According this framework, systemic class 1B 3B drugs is likely determined OATP-mediated hepatic uptake. Class 3A 4 drugs, certain predominantly cleared renal, wherein, OAT1, OCT2, MATE proteins could contribute their active renal secretion. Intestinal efflux uptake largely influence oral 3A, 3B, discuss paradigm applying ECCS framework mapping clinically relevant discovery development; thereby implementing right strategy allow optimization exposure evaluation risk DDIs pharmacogenomics.