Upon investigations on metabolism and pharmacokinetics of 1-(theophyllin-7-yl)-ethyl-2-[2-(chlorophenoxy)-2-methylpropionate] (etofylline clofibrate, ML 1024, Duolip) is reported. As can be seen from in vivo tests in rats and dogs ML 1024 is cleaved to the metabolites clofibric acid and etofylline. This could be further demonstrated in vitro by incubation with lipases and human serum. The pharmacokinetic parameters of the metabolites after oral application of 2 capsules Duolip, corresponding to 500 mg etofylline clofibrate, were evaluated in 7 healthy volunteers. The serum fluctuations of the main metabolites could be adapted to an open two-compartment model (etofylline). The following mean values were found: the invasion half-life is 1 h 4 min for clofibric acid and 1 h 52 min for etofylline. The maximum concentration after approximately 4 h is 22.75 micrograms/ml for clofibric acid and 6.57 micrograms/ml for etofylline. The elimination half-life is 12.12 h for clofibric and 4.33 h for etofylline. Via urine 20 mg clofibric acid and 15.7 mg etofylline were excreted within 8 h. The elimination process after 8 h is not yet terminated.

中文翻译：

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新型抗血脂药依托茶碱氯贝贝酯的代谢和药代动力学

在对1-（茶碱-7-基）-乙基-2- [2-（氯苯氧基）-2-甲基丙酸酯]（依托茶碱氯氟贝特，ML 1024，Duolip）的代谢和药代动力学进行研究的报告中。从大鼠和犬的体内试验中可以看出，ML 1024被裂解为代谢产物氯纤维酸和依托茶碱。通过与脂肪酶和人血清一起孵育，可以进一步证明这一点。在7名健康志愿者中评估了口服2粒Duolip胶囊（相当于500毫克依托茶碱氯贝贝特）后的代谢产物的药代动力学参数。主要代谢物的血清波动可适应开放的两室模型（依托茶碱）。发现以下平均值：氯贝酸的侵袭半衰期为1 h 4 min，而乙磷茶碱的侵袭半衰期为1 h 52 min。大约4小时后，最大浓度为氯纤维酸为22.75微克/毫升，乙苯茶碱为6.57微克/毫升。消除纤维的半衰期为12.12 h，依托茶碱为4.33 h。通过尿液在8 h内排泄20 mg氯纤维酸和15.7 mg依托茶碱。8小时后的消除过程尚未结束。