醋氨酚在6例健康志愿者的药代动力学研究

Study on the pharmacokinetics of acetaminophen in six healthy volunteers

目的 研究结合代谢模型药物醋氨酚 (ac etaminophen ,Ace)在健康人的药代动力学及其尿液中代谢产物的累积排泄量。方法 6例健康志愿者空腹口服醋氨酚 1.0g后 ,定时收集唾液及 2 4h尿液。采用高效液相色谱法 (HPLC) ,测定Ace、葡萄糖醛酸 Ace (GA)和硫酸 Ace (SA)含量。结果 唾液Acet1/2 为 (2 .5 0± 0 .2 9)h ,CL为 (10 .3±1.6 )L·h- 1,k为 0 .2 8± 0 .0 3,AUC为 (98.9±16 .7) μg·h·ml- 1,Vd 为 (44 .4± 16 .5 )L ;2 4h尿液中Ace、GA、SA的含量及三者累积排泄量分别占给药量的 (3.4± 0 .7) %、 (37.5± 10 .2 ) %、 (2 4 .5±15 .5 ) %和 (70 .4± 7.7) %。结论 与国外同类报道比较 ,Acet1/2 延长 2 5 % ,GA累积排泄量仅占其5 0 %。提示肝脏葡萄糖醛酸结合代谢能力低下可能是引起Acet1/2

Aim To study the pharmacokinetics of acetaminophen (Ace) in healthy volunteers and total recovery of its metabolites in urine. Methods 1.0 g Ace was administrated orally in 6 fasted healthy males; saliva and 24 h urine were collected regularly for the determination of Ace, glucuronide Ace (GA) and sulfate Ace (SA) levels by using HPLC. Results Ace in saliva showed that t 1/2 was ( 2.50 ± 0.29) h , CL was ( 10.3 ± 1.6) L·h -1 , k was ( 0.28 ± 0.03 ), AUC was ( 98.9 ± 16.7) μg ·h·ml -1 , V d was ( 44.4 ± 16.5) L ; GA and SA in 24 h urine and in total recovery were ( 3.4 ± 0.7 )%, ( 37.5 ± 10.2 )%, ( 24.5 ± 15.5 )% and ( 70.4 ± 7.7 )% respectively. Conclusions Compared with those reported by researchers in western countries, t 1/2 of Ace prolonged 25% and total elimination was only 50% of theirs. It seemed that low hepatic glucuronide metabolism might be an important factor for prolongation of t 1/2 of Ace.