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.%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72 h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200 ng·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.
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