Li L, Zhang Y
Department of Pharmacology, Beijing Medical University, Beijing 100083.
Yao Xue Xue Bao. 1998 Dec;33(12):891-5.
Diabetic rat model was induced by alloxan. To evaluate CYP2E1 activity indirectly, the activities of aniline dehydroxylase and other drug metabolic enzymes were measured. The pharmacokinetic profile of chlorzoxazone(CZX), a drug probe for CYP2E1, was obtained after a single oral dose of 50 mg.kg-1. The results indicated that diabetes increased aniline dehydroxylase activity by 53%. The Cmax and AUC of chlorzoxazone in diabetic rats were reduced 37% and 34%, respectively. The Tpeak of 6-hydroxychlorzoxazone in diabetic rats was shortened apparently. The hydroxylation index described by the AUC ratio of 6-hydroxychlorzoxazone to chlorzoxazone or the ratio of concentration of 6-hydroxychlorzoxazone to chlorzoxazone, which indicated the ability of hydroxylation, was increased in diabetes. In conclusion, diabetes can induce CYP2E1 activity, suggesting that diabetic patients should be cautious when taking some therapeutic drugs which metabolized by CYP2E1.
用四氧嘧啶诱导建立糖尿病大鼠模型。为间接评估CYP2E1活性，测定了苯胺脱羟酶和其他药物代谢酶的活性。单次口服50 mg·kg-1的CYP2E1药物探针氯唑沙宗（CZX）后，获得其药代动力学特征。结果表明，糖尿病使苯胺脱羟酶活性增加了53%。糖尿病大鼠中氯唑沙宗的Cmax和AUC分别降低了37%和34%。糖尿病大鼠中6-羟基氯唑沙宗的Tpeak明显缩短。由6-羟基氯唑沙宗与氯唑沙宗的AUC比值或6-羟基氯唑沙宗与氯唑沙宗的浓度比值描述的羟基化指数，表明羟基化能力，在糖尿病中增加。总之，糖尿病可诱导CYP2E1活性，提示糖尿病患者在服用某些由CYP2E1代谢的治疗药物时应谨慎。
