Ferner R E, Antsiferov M L, Kelman A W, Alberti K G, Rawlins M D
Wolfson Unit of Clinical Pharmacology, University of Newcastle upon Tyne, UK.
Eur J Clin Pharmacol. 1991;40(2):163-8. doi: 10.1007/BF00280071.
It is uncertain how the hypoglycaemic effect of sulphonylureas varies with drug concentration in patients with non-insulin-dependent diabetes mellitus. The inter-relationship of tolbutamide dosage and concentration, and glucose and insulin concentrations were therefore examined in 54 out-patients (the observational group) and in 20 patients studied under controlled conditions (the experimental group). In the observational group, tolbutamide concentration depended significantly on the daily dose, time from dose to sampling, body weight, and age. Blood glucose and insulin concentration were related, but were independent of tolbutamide concentration. In the experimental group, peak, but not pre-dose, tolbutamide concentration, depended on dose and on body mass index. Fasting and maximum post-prandial blood glucose concentration were positively correlated with maximum tolbutamide concentration, probably because tolbutamide dosage was highest in those with the poorest response. In the subset with a fasting blood glucose concentration of less than 8 mmol.l-1, neither glucose nor insulin concentrations depended significantly on tolbutamide concentrations. Tolbutamide concentration does not directly determine hypoglycaemic response in outpatients, and therapeutic monitoring of drug concentrations would not improve the management of such patients.
在非胰岛素依赖型糖尿病患者中，磺脲类药物的降血糖作用如何随药物浓度变化尚不确定。因此，对54名门诊患者（观察组）和20名在受控条件下研究的患者（实验组）进行了甲苯磺丁脲剂量与浓度、血糖与胰岛素浓度之间相互关系的研究。在观察组中，甲苯磺丁脲浓度显著取决于每日剂量、给药至采样的时间、体重和年龄。血糖和胰岛素浓度相关，但与甲苯磺丁脲浓度无关。在实验组中，甲苯磺丁脲的峰值浓度（而非给药前浓度）取决于剂量和体重指数。空腹和餐后最高血糖浓度与甲苯磺丁脲最高浓度呈正相关，这可能是因为反应最差的患者甲苯磺丁脲剂量最高。在空腹血糖浓度低于8 mmol·l-1的亚组中，血糖和胰岛素浓度均与甲苯磺丁脲浓度无显著相关性。甲苯磺丁脲浓度不能直接决定门诊患者的降血糖反应，对药物浓度进行治疗监测并不能改善此类患者的管理。
