Pharmacokinetics and tissues distribution of metformin in rats

AIM To investigate the distribution and pharmacokinetic properties of metformin in rats. METHODS After a single administration(ip)of metformin with a dose of 100 mg·kg~(-1),the plasma samples from the rats(n=3)were taken at 0,10,20,30,60,120,240,480,and 720 min for determination of the pharmacokinetic parameters of metformin in rat blood.The various organ samples were also taken from another group of animals(n=27,3 rats per time point)for the distribution study of the drug.RESULTS The main pharmacokinetic parameters were as follow:AUC(4676±s171)mg·min·L~(-1),CL(21.4±0.8)mL·min~(-1)·kg~(-1),_(1/2)(50±5)min,t_(max)(20.0±1.0)min,c_(max)(59±4)mg·L~(-1).Metformin were detected in all tissue samples 10 min after administration and could not be tested in liver,lung,spleen and brain 12 h after administration.CONCLUTION The plasma concentration-time curve of metformin revealed that the pharmacok- inetics of metformin in vivo fulfills the one-compartment model.The absorption,clearance with its diffuse distribution in vivo were rapid and the clearance appeared to be mainly via the kidney pathway.Metformin was readily permeable across the blood brain barrier.