Koren G, Sandler A N, Klein J, Whiting W C, Lau L C, Slavchenko P, Daley D
Division of Clinical Pharmacology, Hospital for Sick Children, Toronto, Ontario, Canada.
Clin Pharmacol Ther. 1989 Oct;46(4):458-62. doi: 10.1038/clpt.1989.165.
To establish the relationships between epidural sufentanil analgesia and respiratory effects and to determine the pharmacokinetics of the drug, 22 adult patients undergoing thoracotomy were put into a randomized, double-blind study and received either 30, 50, or 75 micrograms per dose in 20 ml normal saline solution. Repeated doses were given on request for the 24-hour study period. There was a weak but significant nonlinear correlation between length of effective analgesia and the cumulative dose of the drug (r = 0.26, p less than 0.001). In 12 of 22 patients, the maximal length of effective analgesia was reached before the last dose and the effect tended to taper off thereafter. The mean maximal length of effective analgesia was 4.69 +/- 0.32 hours (mean +/- SEM), whereas the length of effective analgesia with the last dose was only 3.34 +/- 0.46 hours (p less than 0.0005). There was a significant correlation between the peak serum concentrations of sufentanil during the dose interval and the length of effective analgesia (r = 0.44, p less than 0.0001). Area under the concentration-time curve was proportional to the size of the epidural dose, and with all three doses tested there was a gradual accumulation of sufentanil in the serum. Mean time-to-peak concentration (tmax) increased with repeated doses (p less than 0.05). Mean serum concentration of sufentanil during periods of slow respiratory rate (0.47 +/- 0.05 ng/ml) was significantly higher than during episodes without adverse respiratory effects (0.37 +/- 0.05 ng/ml, p less than 0.05). The above data suggest that an important part of the analgesic and adverse effects of sufentanil are mediated centrally, after this opioid is absorbed systemically.
为了建立硬膜外舒芬太尼镇痛与呼吸效应之间的关系，并确定该药物的药代动力学，22例接受开胸手术的成年患者被纳入一项随机双盲研究，分别接受每剂量30、50或75微克溶于20毫升生理盐水溶液中的药物。在24小时的研究期间，根据需要重复给药。有效镇痛时长与药物累积剂量之间存在微弱但显著的非线性相关性（r = 0.26，p < 0.001）。22例患者中有12例在最后一剂之前达到了最大有效镇痛时长，此后效果趋于逐渐减弱。有效镇痛的平均最大时长为4.69±0.32小时（平均值±标准误），而最后一剂的有效镇痛时长仅为3.34±0.46小时（p < 0.0005）。剂量间隔期间舒芬太尼的血清峰值浓度与有效镇痛时长之间存在显著相关性（r = 0.44，p < 0.0001）。浓度-时间曲线下面积与硬膜外剂量大小成正比，在所有测试的三种剂量下，舒芬太尼在血清中逐渐蓄积。平均达峰时间（tmax）随重复给药而增加（p < 0.05）。呼吸频率缓慢期间舒芬太尼的平均血清浓度（0.47±0.05纳克/毫升）显著高于无不良呼吸效应发作期间的浓度（0.37±0.05纳克/毫升，p < 0.05）。上述数据表明，舒芬太尼的镇痛和不良反应的一个重要部分是在该阿片类药物全身吸收后由中枢介导的。
