Morgera S, Budde K, Lampe D, Ahnert V, Fritsche L, Kuchinke S, Neumayer H H
Department of Internal Medicine-Nephrology, University Hospital-Charité, Berlin, Germany.
Transpl Int. 1998;11(1):53-7. doi: 10.1007/s001470050102.
We prospectively studied the impact of peritoneal dialysis (PD) on the pharmacokinetics of mycophenolic acid (MPA) in five patients following renal transplantation. Three patients had a glomerular filtration rate (GFR) of less than 10 ml/min and two had a GFR of more than 40 ml/min. Pharmacokinetics of MPA and of its main metabolite, mycophenolic acid glucuronide (MPAG), were studied during two consecutive 12-h periods (with and without PD). After initiation of PD in patients with severe renal impairment (GFR < 10 ml/ min), MPA-area-under-the-concentration-curve (AUC) decreased up to 59% and MPAG-AUC decreased up to 26%. We did not observe any substantial changes in the MPA-AUC or MPAG-AUC of either patient with a GFR above 40 ml/min. Patients with a reduced GFR had much higher MPAG values than patients with a GFR above 40 ml/l; yet, we did not observe any differences in the MPA values. We found a significant inverse correlation between GFR and MPA-AUC (r = 0.81, P < 0.05) and between GFR and MPAG-AUC (r = 0.94, P < 0.01). While MPA was found only in traces in the peritoneal ultrafiltrate, the cumulative amount of MPAG removed by PD reached up to 2 g/ 12 h, representing 1.2 g of MPA. This is the first report describing a reduction in MPA-AUC and MPAG-AUC during PD. Further studies are needed to completely understand the pharmacokinetics of mycophenolate mofetil during PD.
我们前瞻性地研究了腹膜透析(PD)对5例肾移植患者霉酚酸(MPA)药代动力学的影响。3例患者的肾小球滤过率(GFR)低于10 ml/分钟,2例患者的GFR高于40 ml/分钟。在连续两个12小时期间(有和无PD)研究了MPA及其主要代谢产物霉酚酸葡萄糖醛酸苷(MPAG)的药代动力学。在严重肾功能损害(GFR<10 ml/分钟)的患者开始PD后,MPA浓度-时间曲线下面积(AUC)下降高达59%,MPAG-AUC下降高达26%。我们未观察到GFR高于40 ml/分钟的任何一位患者的MPA-AUC或MPAG-AUC有任何实质性变化。GFR降低的患者的MPAG值比GFR高于40 ml/l的患者高得多;然而,我们未观察到MPA值有任何差异。我们发现GFR与MPA-AUC之间存在显著负相关(r = 0.81,P<0.05),GFR与MPAG-AUC之间也存在显著负相关(r = 0.94, P<0.01)。虽然在腹膜超滤液中仅发现痕量的MPA,但PD清除的MPAG累积量高达2 g/12小时,相当于1.2 g的MPA。这是第一份描述PD期间MPA-AUC和MPAG-AUC降低的报告。需要进一步研究以全面了解霉酚酸酯在PD期间的药代动力学。