Pharmacokinetics of mycophenolate mofetil in renal transplant recipients on peritoneal dialysis.
Little is known about the pharmacokinetics of mycophenolatic acid (MPA) in the early posttransplant period after renal transplantation. We studied the impact of peritoneal dialysis on the pharmacokinetics of MPA in 5 patients following renal transplantation (3-6 weeks after transplantation). Three patients had a glomerular filtration rate (GFR) of less than 10 ml/min, 1 patient had a GFR of 32, and 1 of 58 ml/min. Pharmacokinetics of MPA and its main metabolite mycophenolic acid glucuronide (MPAG) were studied on 2 consecutive days (12-hour intervals: with and without peritoneal dialysis). Dosing of MPA was 2 x 1 g/day. MPA and MPAG concentrations were determined by HPLC methods. After initiation of peritoneal dialysis in patients with severe renal impairment (GFR < 10 ml/min) MPA area under the concentration curve (AUC) decreased substantially (15-59%). The calculated clearance of MPA was higher (14.6 vs 8.1 ml/min/kg) on the day of peritoneal dialysis than during the dwell-free day. MPAG-AUC decreased up to 26% in these patients. In both patients with a GFR > 30 ml/min we observed an increase of MPA-AUC on the day of peritoneal dialysis and a decreased MPA clearance. MPAG-AUCs remained stable. Patients with a reduced GFR had much higher MPAG values than patients with a GFR 30 ml/l, however, we did not observe any differences for the MPA levels. We found a significant inverse correlation between GFR and MPAG-AUC (r = 0.91, p < 0.05). While MPA was found only in traces in the peritoneal ultrafiltrate, the cumulative amount of MPAG removed by peritoneal dialysis reached up to 2 g per 12 hours, representing up to 1.2 g of MPA. This is the first report describing a reduction of MPA- and MPAG-AUC during peritoneal dialysis. Further studies are needed to better understand the pharmacokinetics of mycophenolat mofetil during peritoneal dialysis.
Morgera
S
S
Department of Internal Medicine, Nephrology, Charité, Berlin, Germany.
Neumayer
H H
HH
Fritsche
L
L
Kuchinke
S
S
Lampe
D
D
Ahnert
V
V
Bauer
S
S
Mai
I
I
Budde
K
K
D000328:Adult; D000903:Antibiotics, Antineoplastic / Q000493:pharmacokinetics; D019540:Area Under Curve; D005260:Female; D005919:Glomerular Filtration Rate / Q000276:immunology; D005965:Glucuronates / Q000493:pharmacokinetics*; D020719:Glucuronides; D006084:Graft Rejection / Q000517:prevention & control; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D016030:Kidney Transplantation / Q000534:rehabilitation*; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D010530:Peritoneal Dialysis; D011446:Prospective Studies
D000903:Antibiotics, Antineoplastic; D005965:Glucuronates; D020719:Glucuronides; D007166:Immunosuppressive Agents; C113145:mycophenolic acid glucuronide; D009173:Mycophenolic Acid