The Study Of Pharmacokinetics Of Glimepiride In Healthy Chinese Volunteers

Glimepiride(GM) is a newly oral blood-glucose-lowering drug of sulfonylurea class,which is nearly compeletly absorbed after oral administration,and more than 99 percent of the drug is combined with plasma protein.Once GM bonds to 65-KDa protein located on the surface of 3 cell of pancreas islet,that will cause the closing of ATP-K+channel located on the cell membrane and resulting in the membrane's depolarization ?and consequently insulin is released .The conjunction of GM together with the dispertive special sites results in decreasing the time of interaction of GM to it's receptor, thereby the action of GM is 2 or 3 times and dissociation is 8 or 9 times as fast as that of glibenclamide,which make it having less chance to interfece the cardiovascular system. In addition.GM may make the peripheral tissues to improve the sensitivity to insulin,to incease the intape and using of glucose and increase the synthesis of fat and glycogen. At present, glimepiride is substituting other drugs of sulfonylurea gradually and becoming the leading antidiabetic drug. This paper investigated the pharmacokinetic process of glimepiride in heathy Chinese volunteers,the results are as follows:1. A sensitive and selective high performance liquid chromatographic method was developed for determination of glimepiride in human plasam with ultraviolet detection after pre-column derivatization. Glimepiride was well seperated under this method and there was no significant interferential peak so this method is specific for determination of GM. The lowest detection limit was 5ng ml-1 and exhibited good linearity in the rang of 10-400ng ml-1 .The standerd curve wasR=0.0035XC -0.00191(r =0.9996) and the deviation of recovery ratio for this method was lower than 2% RSD between days or within day was lower than 5%. All of those were suitable to requirement of researching pharmacokinetics.2. The concentration-time data in 14 healthy male volunteers after administered 3mg glimepiride conformed to extravascular three-compartment model of first-order kinetics, and T1/2 P was 9.87+4.47h, AUCo-n was 1173.67 +167.82ng.runr1, G?was 202.701+24.819ng.mr', T?was 2.64+0. 54h, Vd/f was 26.09 + 0.54L and CL/f was 43.42+8.92ml.mm'o3 Comparing the pharmacokinetic parameters of healthy Chinese to those of white people , we found the T1/2 of Chinese was about 30% more than that of white people, the Vd/f was about 20% more than that of white people, the CL/f was about 17% lower than that of white people and the dm was about 15% lower than that of white people (P<0.05 ) These differeces show that glimepiride is distributed much extensive and eliminated more slowly so that the Cmax is lower than that in white people,thereby the effective concentration of GM could maitain a longer time.And it will benefit the patients in clinical administration for controling the blood sugar.