【摘要】 目的:研究雷米芬太尼(R)及其体内的主要代谢产物雷米芬太尼酸(RA)在开胸手术后镇痛患者中的药动学,为临床合理安全用药提供依据。方法:20例成年患者纳入本项研究,其中包括肾功能正常者10例(CLcr(72.1±11.5)mL·min-1,n=10),中/重度肾功能损害者10例(CLcr(27.9±14.7)mL·min-1,n=10)。R静脉滴注速度为6μg·kg-1·h-1,持续72h,用药后收集72h内的桡动脉血样本,计算药动学参数。结果:R的药动学在正常组与中/重度肾功能损害组间无显著性差异;在中、重度肾功能损害组,RA的肾清除率下降为正常组的约25%((41.2±16.1)vs.(157±19.5)mL·h-1·kg-1,P<0.001)。R血药浓度达到稳态时,中/重度肾功能损害者对R的代谢比大约为正常者的8倍((115±39.3)vs.(14.3±5.4),P<0.001)。在中/重度肾功能损害者体内,RA的最高浓度接近200ng·mL-1,但未达到产生阿片类药效的血药浓度。结论:肾功能状态对R药动学参数无显著影响;但肾功能受损时,RA在体内易产生蓄积。更多还原

【Abstract】 OBJECTIVE:To study pharmacokinetics of remifentanil (R) and its main metabolite remifentanil acid (RA) in postoperative analgesia patients underwent open-heart surgery,so as to provide reference for rational use of drug in the clinic.METHODS:20 adult patients were included,invovling 10 patients with normal renal function (CLcr (72.1±11.5) mL·min-1,n=10) and 10 patients with moderate/severe renal impairment (CLcr (27.9±14.7) mL·min-1,n=10).Remifentanil was infused for 72 h at rate of 6 μg·kg-1·h-1.Radial artery blood sample within 72 h were collected after administration and pharmacokinetic parameters were calculated.RESULTS:The pharmacokinetics of remifentanil had no significance between normal group and moderate/severe renal impairment group.RA clearance rate of moderate/severe renal impairment group was reduced to about 25% than that of the normal group ((41.2±16.1) vs.(157±19.5) mL·kg-1·h-1,P<0.001).Metabolic ratio of RA in moderate/severe renal impairment group under the condition of remifentanil concentrations at steady state was approximately eight-fold higher than in normal group ((115±39.3) vs.(14.3±5.4),P<0.001).Maximum level of RA approached 200 ng·mL-1 in moderate/severe renal impairment group,which wasn’t associated with the prolongation of μ-opioid effects.CONCLUSION:Renal function of patients doesn’t affect pharmacokinetic parameters of remifentanil.But RA accumulates in patients with moderate/severe impairment.更多还原