茶碱非线性清除的临床考察

Clinical investigation of theophylline nonlinear clearance

目的：对常规剂量时茶碱非线性代谢进行研究。方法：２０例肝肾功能正常，呼吸道疾病患者，给予二个不同剂量的氨茶碱（０．３～０．６ｇ·ｄ－１）治疗，达稳态后，用高效液相色谱法分别测定二个谷浓度值，以Δ％浓度比Δ％剂量≥１．５为判定非线性代谢的标准。结果：有１１例患者出现了非线性代谢，发生率５５％。其药动学常数：Ｖｍ＝７０７．７±１７５．４ｍｇ·ｄ－１，Ｋｍ＝５．８±３．８μｇ·ｍｌ－１。结论：本实验结果对临床更安全的应用氨茶碱有新的提示。

OBJECTIVE:To assess the clinical impact of nonlinearity in theophylline elimination.METHODS:Twenty patients with respiratory diseases and normal hepatic functions were treated with theophylline. Blood samples of patients were collected after oral administration two different dosages( 0.3 ～ 0.6 g·d -1 )to steady states and were determined by HPLC. The ratio of Δ% concentration/Δ% dose≥ 1.5 was used for judging a nonlinear kinetics of theophylline. RESULTS:According to this criterion, 11 of 20(55%)patients were selected for Michaclis Menten kinetics and V m=707.7±175.4 mg·d -1 , K m=5.8±3.8 μg·ml -1 .CONCLUSIONS:If the nonlinearity could occur,the caution is needed with these certain susceptible individuals when using linear kinetics for the dosage modification of theophylline.