Burm A G, Stienstra R, Brouwer R P, Emanuelsson B M, van Kleef J W
Department of Anesthesiology, Leiden University Medical Center, The Netherlands.
Anesthesiology. 2000 Aug;93(2):395-403. doi: 10.1097/00000542-200008000-00017.
Changing plasma protein concentrations may affect the protein binding and pharmacokinetics of drugs in the postoperative phase. Therefore, the authors evaluated the pharmacokinetics of ropivacaine, administered by 72-h epidural infusion to provide postoperative analgesia.
Twenty-eight patients, scheduled for major orthopedic surgery during combined epidural and general anesthesia received a bolus dose of ropivacaine (50 or 75 mg), followed by constant-rate (10 ml/h) epidural infusion of ropivacaine 2 mg/ml (group 1) or 3 mg/ml (group 2). Total and unbound plasma concentrations of ropivacaine and pipecoloxylidide and plasma concentrations of alpha1-acid glycoprotein were determined. In addition, the urinary excretion of ropivacaine and major metabolites was measured.
Total plasma concentrations of ropivacaine increased steadily during the infusion, reaching 2.7 +/- 0.7 and 2.9 +/- 0.5 mg/l in groups 1 and 2 after 72 h constant-rate infusion. Unbound ropivacaine concentrations reached average steady state levels of approximately 0.06 and 0.07 mg/l. Total and unbound concentrations of pipecoloxylidide increased to 1.0 +/- 0.4 and 0.4 +/- 0.2 mg/l (group 1) and 1.2 +/- 0.4 and 0.5 +/- 0.1 mg/l (group 2) after 72 h infusion. alpha1-Acid glycoprotein concentrations initially decreased, but thereafter increased steadily to approximately twice the baseline values.
Postoperative increases in plasma alpha1-acid glycoprotein concentrations enhance the protein binding of ropivacaine and pipecoloxylidide, causing divergence of total and unbound plasma concentrations.
血浆蛋白浓度的变化可能会影响术后阶段药物的蛋白结合及药代动力学。因此，作者评估了通过72小时硬膜外输注罗哌卡因以提供术后镇痛时的药代动力学。
28例计划在硬膜外联合全身麻醉下进行大型骨科手术的患者接受了一剂罗哌卡因（50或75毫克），随后以恒定速率（10毫升/小时）硬膜外输注2毫克/毫升（第1组）或3毫克/毫升（第2组）的罗哌卡因。测定罗哌卡因和哌啶卡因的总血浆浓度及游离血浆浓度，以及α1-酸性糖蛋白的血浆浓度。此外，还测量了罗哌卡因及其主要代谢产物的尿排泄量。
在输注过程中，罗哌卡因的总血浆浓度稳步上升，在第1组和第2组进行72小时恒定速率输注后，分别达到2.7±0.7毫克/升和2.9±0.5毫克/升。游离罗哌卡因浓度达到平均稳态水平，约为0.06毫克/升和0.07毫克/升。输注72小时后，哌啶卡因的总浓度和游离浓度在第1组分别增至1.0±0.4毫克/升和0.4±0.2毫克/升，在第2组分别增至1.2±0.4毫克/升和0.5±0.1毫克/升。α1-酸性糖蛋白浓度最初下降，但随后稳步上升至约为基线值的两倍。
术后血浆α1-酸性糖蛋白浓度的升高增强了罗哌卡因和哌啶卡因的蛋白结合，导致总血浆浓度和游离血浆浓度出现差异。
