Müller H, Gerlach H, Gips H, Richter M, Börner U, Hempelmann G
Anaesthesist. 1986 Apr;35(4):219-25.
In order to demonstrate pharmacokinetic and pharmacodynamic interactions between fentanyl and buprenorphine, 3 groups of patients (n = 30) were compared, receiving either fentanyl (0.005 mg/kg b.w.) or buprenorphine (0.01 mg/kg b.w.) or both opioids as analgesic during surgery for disc protrusion. For a period of 4 h haemodynamic parameters were monitored and blood samples were taken for determination of the following concentrations: ADH, ACTH, cortisol, glucose, unbound glycerol, fentanyl and buprenorphine. Blood gas analyses were performed up to 2 h postoperatively. Although in all groups haemodynamic parameters were constant, there was an increase in factors related to operative stress (cortisol, glucose, unbound glycerol, postoperative acidosis) after the combination of both opioids, while postoperative ventilatory parameters in this group were not improved by the partial agonist buprenorphine. Plasma levels were not affected by combined application, except for a slight elevation of buprenorphine concentrations during additional use of fentanyl. Buprenorphine, at least in higher dosages, seems to antagonize analgesia induced by fentanyl, although respiratory depression is even more pronounced. It may be assumed, that with partial agonists the relation of agonistic and antagonistic activity may be different, depending on the dosage used and on the respective pharmacologic effect observed during investigation.
为了证明芬太尼和丁丙诺啡之间的药代动力学和药效学相互作用,比较了3组患者(每组n = 30),他们在椎间盘突出症手术期间分别接受芬太尼(0.005 mg/kg体重)或丁丙诺啡(0.01 mg/kg体重)或两种阿片类药物作为镇痛药。在4小时内监测血流动力学参数,并采集血样以测定以下浓度:抗利尿激素(ADH)、促肾上腺皮质激素(ACTH)、皮质醇、葡萄糖、游离甘油、芬太尼和丁丙诺啡。术后2小时内进行血气分析。尽管所有组的血流动力学参数均保持恒定,但两种阿片类药物联合使用后,与手术应激相关的因素(皮质醇、葡萄糖、游离甘油、术后酸中毒)有所增加,而该组术后通气参数并未因部分激动剂丁丙诺啡而得到改善。联合应用未影响血浆水平,只是在额外使用芬太尼期间丁丙诺啡浓度略有升高。丁丙诺啡,至少在较高剂量时,似乎拮抗芬太尼诱导的镇痛作用,尽管呼吸抑制更为明显。可以推测,对于部分激动剂,激动和拮抗活性的关系可能不同,这取决于所用剂量以及研究期间观察到的各自药理效应。