雷米芬太尼及其主要代谢物雷米芬太尼酸在术后镇痛患者中的药动学研究

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。

Pharmacokinetic Study of Remifentanil and Its Main Metabolite Remifentanil Acid in Postoperative Analgesia Patients

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,P0.001）.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）,P0.001）.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.