Interindividual differences in the pharmacokinetics(PK)and pharmacodynamics(PD)of metformin

摘要

Metformin is the glucose-lowering drug of choice for the treatment of type 2 diabetes mellitus(T2D).Metformin is also used in the treatment of polycystic ovary syndrome(PCOS).Metformin contains two strong basic nitrogen atoms,and it is therefore 100%double protonated at physiological p H.Thus its passage across cell membranes is highly dependent on cation transport proteins.Metformin is administered orally,and its absorption across the gut mucosa is highly dependent on the organic cation transporter 1(OCT1),OCT3 and the plasma membrane monoamine transporter(PMAT)located in the membrane of the enterocytes.The transport into the hepatocytes,which is the putative site of action,is mainly due to OCT1 in the sinusoidal end of the cells.Metformin is not metabolized but it is excreted unchanged via the kidneys.It is taken up from the blood and into the renal tubular cells by OCT2 located basolat-erally and further transported from the cells into the urine the multidrug and toxin extrusion transporters 1 and 2-K(MATE1 and MATE2-K).The role of gene variants and environmental influences on the PK and PD of metformin will be discussed.