氯诺昔康持续静脉输注用于全髋置换术病人术后镇痛的药代动力学

Pharmacokinetics of lornoxicam infused continuously for postoperative analgesia in patients undergoing total hip replacement

目的 研究氯诺昔康连续静脉输注用于全髋置换术后病人镇痛的药代动力学变化。方法20例行全髋置换术后的病人,氯诺昔康2 mg首剂静脉注射后随机分为两组:Ⅰ组(n=10),连续静脉输注氯诺昔康0.4 mg·2ml-1·h-1;Ⅱ组(n=10),连续静脉输入氯诺昔康0.32 mg·2ml-1·h-1。分别抽取氯诺昔康输注和停止后16个时间点静脉血。用HPLC法测得氯诺昔康及其代谢产物5’-羟氯诺昔康的血浆浓度,并计算其药代动力学参数。结果 根据非房室方法进行药代动力学参数研究显示:氯诺昔康消除半衰期为(4.8±2.1)h(Ⅰ组)和(5.0±2.4)h(Ⅱ组)。L组和U组氯诺昔康血浆稳态浓度(Css)分别为(475±106)ng·ml-1和(393±67)ng·ml-1。输注期间病人血浆浓度保持较小波动。结论氯诺昔康半衰期短,但个体间差异大。

Objective To determine the pharmacokinetics of lornoxicam infused continuously after total hip replacement and the proper way of lornoxicam administration. Methods The study was approved by institutional ethics committe and written consent was obtained. Twenty patients undergoing total hip replacement were enrolled in this study. After operation the patients were randomized to receive continuous infusion of lornoxicam for 24 h at a rate of 0.4 mg·2 ml-1 · h-1 (group 1 n = 10) or 0.32 mg·2ml-1 · h-1 (group 2 n = 10), after a loading dose of lornoxicam 2.0 mg. Blood samples were taken before lornoxicam (baseline), 5, 15 min and 4, 24 h after lornoxicam infusion was started and 1, 2, 4, 8, 12, 16,20,24 h after termination of lornooxicam infusion for determination of plasma concentration of lomoxicam by HPLC. The pharmacokinetic parameters were calculated using computer-assisted non-compartment model. Results There were no significant differences between the two groups with respect to age, body weight and duration of operation. The total amount of lornoxicam consumed in the 24 h was 12 mg (group 1) and 9.5 mg (group 2) respectively. The steady state plasma concentrations (Css) were (475 ± 106) ng·ml-1 (group 1) and (393 ±67) ng·ml-1 (group 2) and blood level of lornoxicam was steady during infusion. Conclusion This study shows that lornoxicam has a relatively short mean elimination half-life and there is considerable individual variation.