Blockade of P-Glycoprotein Decreased the Disposition of Phenformin and Increased Plasma Lactate Level

Biomolecules & Therapeutics
Min-Koo Choi, Im-Sook Song

Abstract

This study aimed to investigate the in vivo relevance of P-glycoprotein (P-gp) in the pharmacokinetics and adverse effect of phenformin. To investigate the involvement of P-gp in the transport of phenformin, a bi-directional transport of phenformin was carried out in LLC-PK1 cells overexpressing P-gp, LLC-PK1-Pgp. Basal to apical transport of phenformin was 3.9-fold greater than apical to basal transport and became saturated with increasing phenformin concentration (2-75 μM) in LLC-PK1-Pgp, suggesting the involvement of P-gp in phenformin transport. Intrinsic clearance mediated by P-gp was 1.9 μL/min while passive diffusion clearance was 0.31 μL/min. Thus, P-gp contributed more to phenformin transport than passive diffusion. To investigate the contribution of P-gp on the pharmacokinetics and adverse effect of phenformin, the effects of verapamil, a P-gp inhibitor, on the pharmacokinetics of phenformin were also examined in rats. The plasma concentrations of phenformin were increased following oral administration of phenformin and intravenous verapamil infusion compared with those administerd phenformin alone. Pharmacokinetic parameters such as Cmax and AUC of phenformin increased and CL/F and Vss/F decreased as a consequence of...Continue Reading

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Jul 11, 2012·The Journal of Pharmacy and Pharmacology·Min-Koo Choi, Im-Sook Song
Apr 16, 2013·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Yoshihisa SogameMikihisa Takano

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Citations

Jan 10, 2020·Drug Development Research·Raghunandan YendapallyBrittany La-Viola
Feb 18, 2017·Clinical Pharmacokinetics·Anton IvanyukThierry Buclin

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Software Mentioned

Statistical Package for the Social Sciences ( SPSS
WinNonlin

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