国产芬太尼在法洛四联症患儿的药代动力学研究

The pharmacokinetics of fentanyl in children with Fallot's tetrad undergoing cardiac surgery

目的 :探讨法洛四联症根治术患儿大剂量应用国产芬太尼的药代动力学。方法 :随机选择法洛四联症根治术患儿 8例 ,芬太尼 10 μg/kg静注后用微量泵持续输注 1μg/(kg·min)至切皮。用GC MS测定血浆芬太尼浓度 ,并计算药代动力学参数。结果 :芬太尼的药代动力学符合开放型三室模型 ,其快速分布半衰期 (t1/2 π)、缓慢分布半衰期 (t1/2 α)和消除半衰期 (t1/2 β)分别为 1.30 ,11.0和 373.5min。总清除率 (Cl)、表观分布容积 (Vd)和中心分布容积 (Vc)分别为 185 .6ml/min ,14.1L/kg和 12 .7L。结论 :法洛四联症患儿心内直视手术国产芬太尼t1/2 β及药物作用时间延长 ,增加手术后再发性呼吸抑制的发生率 ,应注意术后的呼吸管理。

Objective::To study the pharmacokinetics of domestic fentanyl in high dose in children with Fallot's tetralogy.Methods:8 children with Fallot's tetralogy undergoing cardiac surgery were treated with a loading dose of 10μg/kg fentanyl followed by an infusion of 1μg/(kg·min)until starting bypass.The plasma fentanyl level was determined by GC MS and the pharmacokinetic parameters were calculated by use of NONLIN program.Results:Three compartment model was fitted to the pharmacokinetic profile of fentanyl.The pharmacokinetic parameters obtained were t 1/2 π= 1.30 min,t 1/2 α=11.0min,t 1/2 β=373.5min,Cl=185.6ml/min,Vd=14.1L/kg and Vc=12.7L.Conclusion:In children with Fallot's tetralogy,the t 1/2 β and the acting duration of fentanyl were prolonged and the incidence of recurrent ventilatory depression was also increased,therefore after surgery,the respiratory management should be handled with care.