Herman R J, Chaudhary A, Szakacs C B, Woo D, Lane R, Boctor M A
Department of Medicine, Royal University Hospital, University of Saskatchewan, Saskatoon, Canada.
Eur J Clin Pharmacol. 1995;48(3-4):253-8. doi: 10.1007/BF00198307.
The pharmacokinetics of lorazepam was examined in 10 male patients with insulin-dependent diabetes mellitus before and following treatment with neomycin and cholestyramine. Neomycin and cholestyramine were given in an attempt to block the enterohepatic circulation of lorazepam and so to permit an in vivo estimate of hepatic glucuronidation. The volume of distribution and clearance of free lorazepam in diabetic patients were not significantly different from the corresponding estimates in 14 normal controls. Neomycin and cholestyramine increased the clearance of lorazepam by 63% consistent with their effect in non-diabetic controls. However, patients on beef/pork insulin exhibited a greater than normal increase on this interupting regimen (125%), and had a significantly greater neomycin/cholestyramine cycling-interrupted clearance of lorazepam than either normal controls or patients on human insulin (15.4 vs. 6.96 and 7.87 ml.min-1.kg-1). The clearance was correlated positively and significantly with HbA1c and glycated proteins (fructosamine), but only in patients on human insulin. Thus, the pharmacokinetics of lorazepam was not altered in patients with insulin-dependent diabetes mellitus. However, it is possible that there are differences in the rate and extent of hepatic glucuronidation and enterohepatic circulation of lorazepam between patients treated with beef/pork and human insulins and between diabetics treated with beef/pork insulin and non-diabetic controls.
在10名胰岛素依赖型糖尿病男性患者中，研究了在使用新霉素和消胆胺治疗前后劳拉西泮的药代动力学。给予新霉素和消胆胺旨在阻断劳拉西泮的肠肝循环，从而对肝脏葡萄糖醛酸化进行体内评估。糖尿病患者中游离劳拉西泮的分布容积和清除率与14名正常对照者的相应评估值无显著差异。新霉素和消胆胺使劳拉西泮的清除率提高了63%，这与其在非糖尿病对照者中的作用一致。然而，使用牛/猪胰岛素的患者在这种阻断方案下的清除率增加幅度大于正常水平（125%），并且其新霉素/消胆胺循环阻断后的劳拉西泮清除率显著高于正常对照者或使用人胰岛素的患者（分别为15.4 vs. 6.96和7.87 ml·min⁻¹·kg⁻¹）。清除率与糖化血红蛋白（HbA1c）和糖化蛋白（果糖胺）呈正相关且具有显著性，但仅在使用人胰岛素的患者中如此。因此，胰岛素依赖型糖尿病患者中劳拉西泮的药代动力学未发生改变。然而，使用牛/猪胰岛素和人胰岛素治疗的患者之间，以及使用牛/猪胰岛素治疗的糖尿病患者与非糖尿病对照者之间，劳拉西泮的肝脏葡萄糖醛酸化速率和程度以及肠肝循环可能存在差异。
