盐酸阿芬太尼在手术病人中的药代动力学研究

本文进行了两组不同剂量的阿芬太尼在14例手术病人中药代动力学研究。7例一次性iv 80μg·kg~(-1)阿芬太尼,另7例一次性iv 40μg·kg~(-1)。用RIA方法测定0-8 h阿芬太尼的血浆浓度和0-48 h尿中的回收率。研究表明:阿芬太尼在两组病人体内的药代动力学过程均为3室模型。阿芬太尼的初级消除很快,给药后30 min内90％的原型药被消除。病人血浆浓度未发现2次上升现象。二者药-时曲线接近平行,说明阿芬太尼的代谢过程为1级消除。两组阿芬太尼的药代动力学数据经t检验无显著差异(P>0.05)。阿芬太尼的快、慢分布相和消除相的半衰期t_(1/2)π,t_(1/2)α和t_(1/2)β分别为0.71 min±s 0.37 min,11.66 min±s 3.46 min和86.12 min±s 19.15 min;平均总体和中心室的分布容积Vd、Vc分别为34.22L±s 8.27L和4.23L±s 1.72L;平均总体清除率Cl为0.29 L·min~(-1)±s 0.08L·min~(-1)。另外,k_(12)/k_(21)为1.5,k_(13)/k_(31)为3.5,k_(10)大于k_(31)。用药后48 h以内,40μg·kg~(-1)组和80μg·kg~(-1)组的病人尿中排出的原形阿芬太尼分别占总给药量的0.68％±s 0.72％和0.66％±s 0.54％。其肾清除率分别为0.0016 L·min~(-1)±s 0.0011 L·min~(-1)和0.0021 L·min~(-1)±s 0.0015 L·min~(-1)。

THE PHARMACOKINETICS OF ALFENTANIL IN CHINESE FOR SURGICAL OPERATION PATIENTS

The pharmacokinetics of alfentanil, a new short - acting opioid analgesic, has been studied in 14 male Chinese operation patients. 7 patients were given 40μg · kg-1 alfentanil and .7 patients 80μg ·kg-1 alfentanil after an intravenous bolus injection. Plasma concentrations and recovery in urine were measured using a specific radioim-munoassay technique. Plasma concentrations declined triexponentially in both groups. The initial elimination of alfentanil from the plasma was very rapid with 90% of the administered dose leaving the plasma within 30 minutes. The average half - lives for the three phases were similar for both groups. The combined mean(±s) half - lives for the 14 patients for the rapid and slow distribution phases were short(t1/2π = 0. 70 min±s 0. 37 min, t1/2a=11. 66 min±s 3. 46 min) . The elimination half-life,t1/2β was 86.12 min±5 19.15 min which is considerably shorter than that of other opioids. The recovery in urine was 0.67%±s 0.64%. The mean(±s) total body clearance was 0.29 L · min-1 ±s 0.08L · min-1 and the volume of distribution was 0. 497 L · kg-1 ±s0. 132 L · kg-1. The latter is considerably less than reported values for the chemically related drug, fentanyl, and suggests that alfentanil may have a lower tissue binding affinity than fentanyl. The rapid elimination and short duration of clinical action suggest the feasibility of repeated administration of alfentanil and its use by continuous intravenous infusion.