Pharmacokinetics of mycophenolate mofetil in renal transplant recipients on peritoneal dialysis. 1998

S Morgera, and H H Neumayer, and L Fritsche, and S Kuchinke, and D Lampe, and V Ahnert, and S Bauer, and I Mai, and K Budde
Department of Internal Medicine, Nephrology, Charité, Berlin, Germany.

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.

UI MeSH Term Description Entries
D007166 Immunosuppressive Agents Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of T-CELLS or by inhibiting the activation of HELPER CELLS. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of INTERLEUKINS and other CYTOKINES are emerging. Immunosuppressant,Immunosuppressive Agent,Immunosuppressants,Agent, Immunosuppressive,Agents, Immunosuppressive
D008297 Male Males
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D009173 Mycophenolic Acid Compound derived from Penicillium stoloniferum and related species. It blocks de novo biosynthesis of purine nucleotides by inhibition of the enzyme inosine monophosphate dehydrogenase (IMP DEHYDROGENASE). Mycophenolic acid exerts selective effects on the immune system in which it prevents the proliferation of T-CELLS, LYMPHOCYTES, and the formation of antibodies from B-CELLS. It may also inhibit recruitment of LEUKOCYTES to sites of INFLAMMATION. Cellcept,Mycophenolate Mofetil,Mycophenolate Mofetil Hydrochloride,Mycophenolate Sodium,Mycophenolic Acid Morpholinoethyl Ester,Myfortic,RS 61443,RS-61443,Sodium Mycophenolate,Mofetil Hydrochloride, Mycophenolate,Mofetil, Mycophenolate,Mycophenolate, Sodium,RS61443
D010530 Peritoneal Dialysis Dialysis fluid being introduced into and removed from the peritoneal cavity as either a continuous or an intermittent procedure. Dialyses, Peritoneal,Dialysis, Peritoneal,Peritoneal Dialyses
D011446 Prospective Studies Observation of a population for a sufficient number of persons over a sufficient number of years to generate incidence or mortality rates subsequent to the selection of the study group. Prospective Study,Studies, Prospective,Study, Prospective
D005260 Female Females
D005919 Glomerular Filtration Rate The volume of water filtered out of plasma through glomerular capillary walls into Bowman's capsules per unit of time. It is considered to be equivalent to INULIN clearance. Filtration Rate, Glomerular,Filtration Rates, Glomerular,Glomerular Filtration Rates,Rate, Glomerular Filtration,Rates, Glomerular Filtration
D005965 Glucuronates Derivatives of GLUCURONIC ACID. Included under this heading are a broad variety of acid forms, salts, esters, and amides that include the 6-carboxy glucose structure. Glucosiduronates,Glucuronic Acids,Acids, Glucuronic
D006084 Graft Rejection An immune response with both cellular and humoral components, directed against an allogeneic transplant, whose tissue antigens are not compatible with those of the recipient. Transplant Rejection,Rejection, Transplant,Transplantation Rejection,Graft Rejections,Rejection, Graft,Rejection, Transplantation,Rejections, Graft,Rejections, Transplant,Rejections, Transplantation,Transplant Rejections,Transplantation Rejections

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