余自成, 陈皓, 张伟霞, 周佩军, 周光文, 陈红专. 霉酚酸在肝移植病人体内的药代动力学研究J. 药学学报, 2006, 41(12): 1157-1160.
引用本文: 余自成, 陈皓, 张伟霞, 周佩军, 周光文, 陈红专. 霉酚酸在肝移植病人体内的药代动力学研究J. 药学学报, 2006, 41(12): 1157-1160.
YU Zi-cheng, CHEN Hao, ZHANG Wei-xia, ZHOU Pei-jun, ZHOU Guang-wen, CHEN Hong-zhuan. Pharmacokinetics of mycophenolic acid in Chinese patients with liver transplantJ. Acta Pharmaceutica Sinica, 2006, 41(12): 1157-1160.
Citation: YU Zi-cheng, CHEN Hao, ZHANG Wei-xia, ZHOU Pei-jun, ZHOU Guang-wen, CHEN Hong-zhuan. Pharmacokinetics of mycophenolic acid in Chinese patients with liver transplantJ. Acta Pharmaceutica Sinica, 2006, 41(12): 1157-1160.

霉酚酸在肝移植病人体内的药代动力学研究

Pharmacokinetics of mycophenolic acid in Chinese patients with liver transplant

  • 摘要: 目的研究免疫抑制剂霉酚酸酯(MMF)的活性代谢物霉酚酸(MPA)在肝移植病人体内的药代动力学。方法38例肝移植病人(男30例,女8例)术后早期按推荐剂量(每次1.0 g,每天两次)口服MMF达稳态,在给予一个早晨的剂量(1.0 g)后,在1个给药间隔内,于给药前及给药后不同时间点采血,用HPLC法测定MPA血药浓度,用3P97软件计算药代动力学参数。结果病人口服MMF后,血浆MPA浓度在给药后0.5~6.0 h内达峰值,部分病人在给药后4~12 h出现第2个小峰,血药峰浓度(Cmax)和药-时曲线下面积(AUC0-12 h)均值分别为(12±7) μg·mL-1和(44±16) μg·h·mL-1,病人个体间存在较大差异。结论MPA在肝移植病人体内的药代动力学存在较大个体差异,提示在临床用药时需要监测MPA血药浓度,进行个体化给药。

     

    Abstract: AimTo investigate the pharmacokinetics of mycophenolic acid (MPA), an active metabolite of mycophenolate mofetil (MMF) in Chinese adult liver transplant patients. MethodsThirty-eight liver transplant patients (male 30, female 8) receiving MMF 1.0 g, twice daily in accordance with the recommended regimen were included in this study. Plasma MPA concentrations were measured by high performance liquid chromatography at 0.5, 1, 1.5, 2, 4, 6, 8, 10 and 12 h after the administration of a single dose. Pharmacokinetic parameters were calculated with 3P97 software. ResultsThe plasma MPA concentration-time curve was characterized with an early sharp peak reached at 0.5-6.0 h after oral administration. And in some patients there was a small second peak due to enterohepatic circulation of mycophenolic acid glucuronide (MPAG), which underwent deglucuronidation and re-absorption as MPA at 4 to 12 h postdose. The mean peak plasma concentration (Cmax) and area under concentration-time curve (AUC0-12 h)were (12±7) μg·mL-1 and (44±16) μg·h·mL-1, respectively. However, a large variability of pharmacokinetic parameters existed in these patients. ConclusionIn view of the inter-individual variability of MMF pharmacokinetics, plasma MPA concentration should be monitored routinely after MMF administration for individual patient.

     

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