盐酸美沙酮口服液在中国美沙酮维持治疗患者体内药动学特征

Pharmacokinetic characteristics of methadone hydrochloride oral solutions in Chinese methadone maintenance treatment patients

目的建立盐酸美沙酮(MTD)人体内血药浓度的测定方法 ,并对口服MTD口服液后的美沙酮维持治疗患者(MMTPs)体内的药动学过程进行研究。方法采用Agilent ZORBAX SB-C_(18)(250mm×4.6 mm,5μm)色谱柱,以乙腈-磷酸盐缓冲液(pH 2.5)=32:68(V/V)为流动相,流速1.50 mL·min^(-1),检测波长206 nm,盐酸苯海索为内标,对血浆中的MTD浓度进行检测。8名MMTPs口服MTD口服液80 mg,分别于服药前和服药后1、2、3、4、6、8、12、24 h采集血样,测定血浆中MTD的浓度,并采用3P97药动学软件对试验数据进行处理,计算有关药动学参数。结果在0.10～10.00 mg·L^(-1)内,MTD与内标峰面积的比值与浓度之间呈良好的线性关系(r=0.999 6)。日内及日间精密度(RSD)和回收率均符合要求。MTD药-时曲线经拟合符合二室模型,主要参数:ρ_(max)(623.13 4-231.06)μg·L^(-1);t_(max)为(2.764±1.13)h;AUC_(0→24h)为(9 569.56±3 294.88)μg·h·L^(-1);AUC_(0→∞)为(21 522.61±10 825.36)μg·h·L~*(-1);t_(1/2)为(23.95±13.61)h。结论本试验建立的检测人血浆中MTD含量的HPLC法,适用性强,重复性好,操作简单,快速准确,成本低廉,可用于MTD药动学的研究;MTD药动学特征和参数在个体间存在较大差异,临床治疗中应实施个体化治疗方案。

AIM To develop a HPLC method for the determination of methadone（MTD） hydrochloride in human plasma, and investigate the pharmacokinetic characteristics of methadone oral solutions in Chinese methadone maintenance treatment patients（MMTPs）. METHODS Liqiud chromatography was performed on Agilent ZORBAX SB- Cl8 column （250 mm × 4.6 mm, 5μm）. The mobile phase consisted of acetonitrile-phosphate buffer（ pH 2.5） = 32： 68 （ V/V ）. The flow rate was 1.50 mL·min^-1 and the UV detection wavelength was 206 nm. The internal standard was trihexyphenidyl hydrochloride. The eight MMTPs were administrated with a single oral dose of 80 mg MTD. Blood samples were drawn from the vein before taking the medicine and at 1,2,3,4,6,8,12 and 24 h after taking the medicine.The concentration of MTD in plasma was detected by HPLC. The data of plasma concentration were precessed and the pharmacokinetic parameters were calculated by 3P97 software. RESULTS The linearity of calibrated curves of plasma sample was in the range of 0.1 - 10 mg·min^-1（ r = 0.999 6） .The recoveries and precision conformed to the requirements. The mean plasma con-centration-time curve of MTD was coincided with two-compartment model. The main parameters were as follows： pmax was （ 623.13± 231.06）μg·L·-1 ; t max Was （2.76 ± 1. 13） h ; AUC0→24h was （9 569.56 ± 3 294.88）μg·h·L^-1 ; AUC0→∞ was （21 522.61± 10 825.36） μg·h·L^-1 ; tl/2 was（23.95± 13.61）h. CONCLUSION The method is demonstrated to be applicable, repeatable, efticient, cheap and simple to operate, and could be used for MTD pharmacokinetic studies. MTD has significant individual differences. Individual dose regimens should be used in the clinical treatment.