Sobiak Joanna, Resztak Matylda, Głyda Maciej, Szczepaniak Paulina, Chrzanowska Maria
Department of Physical Pharmacy and Pharmacokinetics, Poznan University of Medical Sciences, 6 Święcickiego Street, 60-781, Poznań, Poland.
Department of Transplantology and General Surgery, Poznań District Hospital, 7/19 Juraszów Street, 60-479, Poznań, Poland.
Eur J Drug Metab Pharmacokinet. 2016 Aug;41(4):331-8. doi: 10.1007/s13318-015-0262-9. Epub 2015 Feb 7.
We assessed the relations between MPA, free MPA (fMPA) and MPA glucuronide (MPAG) pharmacokinetics and the clinical condition of renal transplant recipients treated with EC-MPS and tacrolimus (Tac) in the first post-transplant year. In 18 adult patients blood samples were collected up to 12 h after EC-MPS oral administration. EC-MPS metabolites' plasma concentrations were determined using validated HPLC methods. All patients reached MPA area under the time-concentration curve (AUC0-12) above 30 µg h/mL. Most of the MPA, fMPA and all MPAG concentrations correlated significantly with respective AUC0-12 values. Some fMPA and all MPAG pharmacokinetic parameters correlated negatively with creatinine clearance and positively with creatinine concentration, whereas no such correlation was observed for MPA. Lower hemoglobin concentrations were observed in patients with higher MPA or fMPA C 0. The significant correlations between MPA C 3 as well as MPA C 4 and MPA AUC0-4 and MPA AUC0-12 may be of importance in further studies including larger number of patients in regard to establishing LSS. In patients treated with EC-MPS and Tac, monitoring MPA C 0 may be important, as too high MPA C 0 may contribute to anemia onset. In EC-MPS treated patients, MPAG concentration is related to renal function as MPAG pharmacokinetics were higher in patients with renal impairment.
我们评估了霉酚酸(MPA)、游离霉酚酸(fMPA)和霉酚酸葡萄糖醛酸苷(MPAG)的药代动力学与接受肠溶型吗替麦考酚酯(EC-MPS)和他克莫司(Tac)治疗的肾移植受者在移植后第一年临床状况之间的关系。在18例成年患者中,于口服EC-MPS后12小时内采集血样。采用经过验证的高效液相色谱法测定EC-MPS代谢产物的血浆浓度。所有患者的MPA时间-浓度曲线下面积(AUC0-12)均达到30µg·h/mL以上。大多数MPA、fMPA和所有MPAG浓度与各自的AUC0-12值显著相关。一些fMPA和所有MPAG药代动力学参数与肌酐清除率呈负相关,与肌酐浓度呈正相关,而MPA未观察到此类相关性。MPA或fMPA C0较高的患者血红蛋白浓度较低。MPA C3以及MPA C4与MPA AUC0-4和MPA AUC0-12之间的显著相关性在进一步研究中可能很重要,这些研究包括更多患者以建立最低有效浓度(LSS)。在接受EC-MPS和Tac治疗的患者中,监测MPA C0可能很重要,因为过高的MPA C0可能导致贫血的发生。在接受EC-MPS治疗的患者中,MPAG浓度与肾功能相关,因为肾功能损害患者的MPAG药代动力学较高。