PHARMACOKINETIC AND PHARMACODYNAMIC STUDIES OF GLIBENCLAMIDE IN NONINSULIN DEPENDENT DIABETES-MELLITUS
PHARMACOKINETIC AND PHARMACODYNAMIC STUDIES OF GLIBENCLAMIDE IN NONINSULIN DEPENDENT DIABETES-MELLITUS
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DOI：
10.1111/j.1365-2125.1990.tb03688.x
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发表时间：
1990-06-01
影响因子：
3.4
通讯作者：
RODGERS, AV
中科院分区：
文献类型：
--
作者：
COPPACK, SW;LANT, AF;RODGERS, AV
1.在31例住院糖尿病患者和79例门诊糖尿病患者中研究了口服格列本脲的药代动力学和药效学特性。2.研究发现，早餐对格列本脲的动力学行为或该药物对血糖利用的影响无显著影响。3. 20 mg给药后格列本脲动力学的时间过程通过二室开放模型充分描述，得到平均半衰期为3.3 ±。1.5 h（t1/2，λ 1）和9.7 ±. 1.2（t1/2，z）分别为初始和终末消除相。4.在肾和肝功能正常、连续接受格列本脲治疗并在8-12周后再次激发的患者中，未发生显著蓄积或动力学特征变化。5.尽管药物吸收存在个体间差异，但在5-20 mg剂量范围内，血浆峰浓度（Cmax）和血浆浓度-时间曲线下面积（AUC（0-24））具有剂量依赖性。在葡萄糖利用方面未观察到显著的剂量-反应行为，表明使用剂量高于5 mg/天的格列本脲几乎没有临床获益。6.比较5 mg和10 mg剂量给药后不同时间段的血浆格列本脲浓度，结果显示，门诊患者的范围比接受相同剂量药物治疗的年龄、性别匹配的住院患者的范围更宽。门诊患者在给药后8小时内所有时间段达到的平均血浆药物浓度均高于住院患者，表明患者在预期到诊所就诊时有“过度依从”的趋势。
1. The pharmacokinetic and pharmacodynamic properties of oral glibenclamide have been studied in 31 hospitalised in-patients and 79 ambulant out-patients with diabetes mellitus. 2. Breakfast was found to have no significant influence on the kinetic behaviour of glibenclamide or on the effect of this drug on blood glucose utilisation. 3. The time course of glibenclamide kinetics after 20 mg dosing was adequately described by a two-compartment open model, yielding mean half-lives of 3.3 .+-. 1.5 h (t1/2, .lambda.1) and 9.7 .+-. 1.2 (t1/2,z) for the initial and terminal elimination phases respectively. 4. No significant accumulation or change in kinetic profile occurred in patients who had normal renal and hepatic function, were treated continuously with glibenclamide, and then rechallenged after 8-12 weeks. 5. Despite inter-individual variations in drug absorption, peak plasma concentrations (Cmax) and the area under the plasma concentration-time curve (AUC(0-24)) were dose-dependent over the dose range 5-20 mg. No significant dose-response behaviour was observed in respect of glucose utilisation, suggesting that there is little clinical benefit in using doses of glibenclamide above 5 mg day-1. 6. Comparison of plasma glibenclamide concentrations at different time-bands following doses of 5 and 10 mg showed a wider range in ambulant out-patients than in age-, sex-matched in-patients treated with the same dosages of drugs. Mean plasma drug concentrations attained at all time bands up to 8 h after dosing were higher in out-patients than in in-patients, suggesting a tendency to ''over-compliance'' by patients in anticipation of attendance at clinic.