Uptake and dispersion of metformin in the isolated perfused rat liver.

摘要: Although metformin is a widely used oral antihyperglycaemic, the exact mechanisms of its cellular uptake and action remain obscure. In this study hepatic extraction disposition kinetics were investigated by use an isolated in-situ rat liver preparation. The was perfused in single-pass mode with protein-free Krebs bicarbonate medium at flow rate 20 mL min(-1). During constant infusion 1 mg L(-1) hydrochloride approached equilibrium within 10 min. steady-state availability, F, determined from ratio outflow concentration to input concentration, 0.99+/-0.02 (mean +/- s.d., n = 4). profile resulting bolus injection 25 microg into portal vein, had sharp peak then slower declining terminal phase. mean transit time (MTT; 49.5+/-14.5, 6) normalized variance (CV2; 4.13+/-0.05) times estimated numerical integration statistical moments data. volume distribution (1.58+/-0.28 (g liver)(-1)) MTT. greater than water space liver, indicating that enters aqueous becomes distributed among components. magnitude CV2 for vascular marker sucrose, suggesting tissue not instantaneous. conclusion, rate-limited permeability barrier. accumulated organ does extract it.