枸橼酸芬太尼在中国手术病人中的药代动力学研究

PHARMACOKINETICS OF FENTANYL IN CHINESE PATIENTS DURING OPERATION

16例手术病人随机分两组,8例一次静脉推注20μg/kg进口芬太尼,另8例一次静脉推注20μg/kg国产芬太尼.用RIA法测定0-12 h的血药浓度和0-48 h的回收率.研究结果表明,芬太尼在病人体内的药代动力学模型为三室模型.芬太尼入血后血浆浓度下降迅速,10min时已有90%以上的入血药物被排除.药-时曲线显示,芬太尼在消除过程中血浆浓度有二次增加现象,主要是因为此药在人体存在肝肠循环.两组病人的T_(1/2π) .和T_(1/2α),T_(1/2)β分别为 2.00±1.24 min,27.56±43.09min,334.35=141.96min(比利时药组)和 1.59±0.64min,12.74±6.61min,301.61±70.15min(国产药组).Cls和Clr分别为1.18±0.33 l/min,0.07±0.03 l/min(比利时药组)和0.73±0.38 l/min,0.03±0.02 l/min.从结果看,两组主要药代动力学参数是相似的.注射芬太尼48h以内,尿中回收原型芬太尼占给药剂量的6.66±2.84%(比利时药组)和3.80±1.73%(国产药组).

The Pharmacokinetics of fentanyl, a highly lipophilic analgesic, were studied in 16 Chinese patients during operation. Eight patients were given 20 μg /kg fentanyl produced by Belgian Janssen; the other patients were given 20 μg / kg fentanyl produced in China as an intravenous bolus injection. Plasma concentration and recovery in urine were measured using RIA technique. The results of this study demonstrate that the pharmacokinetics of fentanyl can be described by a three compartment model, with the plasma concentration declining triexponentially in both groups. Fentanyl concentrations fell rapidly and 90% of the dose was eliminated from the plasma in 10 mins. The half - lives of the rapid and slow distribution phases were short (T1/2π= 2.00 ± 1.24 min, T1/2α = 27.56±43.08 min(Belgium) and T1/2π = 1. 59 ±0. 64 min,T1/2α= 12.74 ± 6.61 min(China). The elimination half-lives, T1/2β was 334.35 ± 141.96 min(Belgium) and 301.61± 70.15 min (China). The pharmacokinetic parameters were similar between the two groups. The total volume of distribution and apparent volume of the central compartment distribution were 516. 55±134. 301, 26. 67± 6.01 1 (Belgium)and 305.62 ± 105.24 1,23.28 ± 10.06 l(China) respectively. The total body clearance and renal clearance were 1. 18±0. 33 l/min, 0.07±0.03 l/ min(Belgium) and 0.73 ±0. 38 l/min, 0. 03 ± 0.02 l/ min(China) respectively. The apparent transfer rate constants between the central compartment and compartment 2 were similar(k12 and k21), wheras the rate constant k13 was 10 times greater than k31. The second peak were found during the elimination phase.