Fujii T, Nakamura K, Furukawa H, Watanabe M, Kuwashima J, Miyazaki H, Kawashima K, Kuzuya T
Arzneimittelforschung. 1983;33(11):1535-7.
Possible drug interaction in clinical use of a hypoglycemic sulfonylurea, gliclazide, was examined by two measures: its binding to protein in vitro and its hypoglycemic effect in vitro in the presence of other therapeutic agents. Binding of radiolabeled sulfonylureas to human serum albumin at its physiological concentration was determined by ultrafiltration in the presence of other agents. The concentrations of all agents examined were at their therapeutic (i.e., clinically observable) levels in the blood. Protein binding of [3H]gliclazide and [14C]tolbutamide was modified by salicylic acid and phenylbutazone but not by tolmetin, warfarin and propranolol. Binding of [3H]glibenclamide was not influenced by these agents under conditions employed. Blood glucose lowering effect of sulfonylureas was studied in rats to which other agents were given. The hypoglycemic effect of gliclazide and chlorpropamide was enhanced by concomitant administration of acetylsalicylic acid and phenylbutazone but not by dicumarol and warfarin. The enhancement of hypoglycemic effect is likely to result from the interaction of protein binding between the drugs.
其在体外与蛋白质的结合以及在其他治疗药物存在下的体外降血糖作用。通过在其他药物存在的情况下进行超滤，测定放射性标记磺脲类药物在其生理浓度下与人血清白蛋白的结合。所检测的所有药物在血液中的浓度均处于其治疗（即临床可观察到）水平。[3H]格列齐特和[14C]甲苯磺丁脲的蛋白质结合受到水杨酸和保泰松的影响，但不受托美丁、华法林和普萘洛尔的影响。在所采用的条件下，[3H]格列本脲的结合不受这些药物的影响。在给予其他药物的大鼠中研究了磺脲类药物的降血糖作用。同时给予乙酰水杨酸和保泰松可增强格列齐特和氯磺丙脲的降血糖作用，但双香豆素和华法林则无此作用。降血糖作用的增强可能是由于药物之间蛋白质结合的相互作用所致。
