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Mycophenolate mofetil pharmacokinetics in renal transplant recipients on peritoneal dialysis
1Department of Internal Medicine-Nephrology, University Hospital-Charité, Berlin, Germany.
Abstract:
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.
Insights
Peritoneal dialysis (PD) significantly reduces mycophenolic acid (MPA) and its metabolite mycophenolic acid glucuronide (MPAG) levels in kidney transplant patients with impaired renal function. This highlights the need for dose adjustments in patients undergoing PD.
Area of Science:
- Nephrology
- Pharmacology
- Transplantation Medicine
Background:
- Mycophenolate mofetil (MMF) is a key immunosuppressant post-renal transplant.
- Its pharmacokinetics, particularly mycophenolic acid (MPA) and its glucuronide metabolite (MPAG), can be affected by renal function.
- The impact of peritoneal dialysis (PD) on MMF pharmacokinetics is not well-established.
Purpose of the Study:
- To investigate the effect of peritoneal dialysis (PD) on the pharmacokinetics of mycophenolic acid (MPA) and its metabolite, mycophenolic acid glucuronide (MPAG), in renal transplant recipients.
- To assess the influence of varying glomerular filtration rates (GFR) on these pharmacokinetic changes during PD.
Main Methods:
- Prospective study involving five renal transplant patients.
- Pharmacokinetic analysis of MPA and MPAG during 12-hour periods with and without PD.
- Patients categorized by GFR: <10 ml/min (n=3) and >40 ml/min (n=2).
Main Results:
- PD initiation led to a significant decrease in MPA-area-under-the-curve (AUC) by up to 59% and MPAG-AUC by up to 26% in patients with GFR < 10 ml/min.
- No substantial changes in MPA-AUC or MPAG-AUC were observed in patients with GFR > 40 ml/min.
- A strong inverse correlation was found between GFR and both MPA-AUC (r=0.81) and MPAG-AUC (r=0.94).
- MPAG was significantly removed by PD (up to 2 g/12h), while MPA was found only in traces.
Conclusions:
- Peritoneal dialysis significantly impacts MPA and MPAG pharmacokinetics, particularly in renal transplant recipients with severe renal impairment.
- The substantial removal of MPAG via PD suggests a need for careful monitoring and potential dose adjustments of MMF in these patients.
- Further research is warranted to fully elucidate the pharmacokinetics of MMF during PD.