美西律正常人药代动力学及其血药浓度与疗效关系的研究

MEXILETINE PHARMACOKINETICS IN HEALTHY VOLUNTEERS AND THE CORRELATION OF MEXILETINE PLASMA CONCENTRATIONS WITH ITS THERAPEUTIC EFFECTS IN PATIENTS

本文报告美西律正常人药代动力学及其血药浓度与疗效关系的研究。血浆药物浓度用二硫化碳衍生化气相色谱法测定。六名健康志愿者,单次静注美西律(100mg/每人)后的药时曲线经计算机以非线性最小二乘法自动拟合,符合三室开放模型。总药时方程为:C_t=079e^(-54.326t)+0.19e^(-3.202t)+0.23e^(-0.082t)。主要药代动力学检数:快分布相半衰期t1/2pi=0.011±0.007h慢分布相半衰期t1/2α=0.218±0.065h;消除半衰期t1/2β=8.156±1.682h;中央室分布容积VL=1.478±O.555l/kg;机体表观分布容积VB=6.984±1.115l/kg;清除率CLB=0.555±0.058 l/kg/h。对临床17例室性早搏患者的用药研究表明,美西律治疗血药浓度为0.3—1.7mg/l;剂量7.5—10mg/kg/d对大部分患者有效;首剂负荷量可使美西律快而有效地发挥疗效。

Mexiletine is an effective agent for the treatment and pro-phylaxis of ventricular arrhythmias. It 's similar to lidocaine in structureand electrophysiological properties. In this study, mexiletine pharmacoki-netics in healthy volunteers and the correlation of mexiletine plasma con-centrations with its therapeutic effects have been investigated. Mexiletinewas given to 7 healthy volunteers as an intravenous injection of 100mg. Theresults showed that mexiletine is the drug with open three-compartmentmodel. Its mean half life of fast and low distribution phases are 0.011±0.007 and 0.218 ±0. 065 h respectively. The elimination half life is 8. 156±1 .682 h. The apparent distribution volume of central compartment is 1 .478±0. 555 l/kg. Body apparent volum of distribution is 6. 884±1. l5 l/kg.Seventeen patients with ventricular arrhythmias were treated with oralmexiletine. The therapeutic plasma concentration of mexiletine is 0. 3-1. 7mg/l, which can be obtained with the dose of 7. 5-10 mg/kg/d. Aloading dose can provide rapid and reliable control of ventriculararrhythmais.