米利酮在慢性肺心病急性发作期患者中的药动学研究

 对１２例慢性肺心病急性发作期患者，均以静脉注射负荷剂量（５０μｇ·ｋｇ￣（－１））继以静滴（每分钟０．５μｇ·ｋｇ￣（－１））维持４ｈ给予米利酮后进行药动学分析。其血药浓度采用ＨＰＬＣ测定，线性范围１０～３２０ｎｇ·ｍｌ￣（－１），回收率９８．８％～１０６．７％，日内、日间ＲＳＤ分别为３．９５％～４．７４％，４．２４％～６．３７％，最低检出限为４ｎｇ·ｍｌ￣（－１）。以Ｔｕｒｂｏ一ＢＡＳＩＣ语言编制程序在３８６／３３兼容机上进行数据处理，求出药动学参数。药时曲线经计算机自动拟合后，９例患者符合二室模型，求得的ＡＵＣ为６３３．６±１７７．７ｎｇ·ｍ１￣（－１）·ｈ，清除半衰期为１．５９±０．７２ｈ，血浆清除率为１５．８８±２．７６Ｌ·ｈ￣（－１），药物分布容积为１４．３３±５．３４Ｌ．另外３例患者符合一室模型，其ＡＵＣ为８７４．４±２７５．８ｎｇ·ｍｌ￣（－１）·ｈ，清除半衰期为１．５４±０．５４ｈ，血浆清除率为１３．０６±６．６７Ｌ·ｈ￣（－１），分布容积为２５．９±４．０９Ｌ。此外，米利酮的降低肺动脉压的作用与血药浓度呈依赖性变化。

Pharmacokinetics of milrione in cardio-pulmonary decompensatedchronic cor pulmonale

Pharmacokinetics of milrione was studied in 12 titled patients after intravenous in-fusion in the single dose of 50 μg·kg￣(-1) and then in the dose of 0.5 μg·kg￣(-1)· min￣(-1) lasting 4hours。 The blood drug concentration was measured by HPLC. The calibration curve was linear inthe range from 10 ng·ml￣(-1) to 320 ng·ml￣(-1),with r=0. 9995.The analytical recovery of milrionefrom plasma was 98.8%～106.7%。 The relative standard deviation for within-day and betweenday was 3. 95%～4. 74%and 4. 24%～6.37%respectively. The detection limit of this methodwas 4 ng·ml￣(-1). The data were disposed with Turbo-BASIC language procedure in 386/33 com-puter. The plasma drug concentration-time curve of 9 patients exhibited two compartment model. AUC was 633.6±177.7ng·ml￣(-1)·h￣(-1) and the mean T1/2β was 1.59±0.72 h.The plasma drugconcentration-time curve of other 3 patients exhibited one compartment model,AUC was 874.4±275.8ng·ml￣(-1) ·h￣(-1) and the mean T1/2 was 1.54±0.54 hour.Meanwhile,the action of de-creasing pulmonary artery pressure was related to the variations of the blood drug concentration。