The Importance of Incorporating OCT2 Plasma Membrane Expression and Membrane Potential in IVIVE of Metformin Renal Secretory Clearance

• Published in: Drug metabolism and disposition Vol. 46; no. 10; pp. 1441 - 1445
• Main Authors: Kumar, Vineet, Yin, Jia, Billington, Sarah, Prasad, Bhagwat, Brown, Colin D.A., Wang, Joanne, Unadkat, Jashvant D.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01.10.2018; American Society for Pharmacology and Experimental Therapeutics, Inc; The American Society for Pharmacology and Experimental Therapeutics
• Subjects: Biological Transport; Biotinylation; Carbon 14; Cell Line; Epithelial cells; Humans; In vivo methods and tests; Kidney - metabolism; Kidney - physiology; Kidneys; Membrane potential; Membrane Potentials; Membranes; Metabolic Clearance Rate; Metformin; Metformin - metabolism; Oct-2 protein; Organic Cation Transporter 2 - metabolism; Plasma; Proteins; Proteomics; Renal cortex; CLr,sec; KRH; BCA; LC-MS/MS; sulfo-NHS-SS-Biotin; DTT; OCT2; IVIVE; SIL; DPBS

Transporter expression, determined by quantitative proteomics, together with PBPK models is a promising approach for in vitro-to-in vivo extrapolation (IVIVE) of transporter-mediated drug clearance. OCT2-expressing HEK293 and MDCKII cells were used to predict in vivo renal secretory clearance (CLr,s...