Comparison of the Incidence of Diarrhea in Renal Transplant Patients with or without Mycophenolate Mofetil Administration

Kobayashi, Mariko; Kobayashi, Mikako; Shinmoto, Hiroshi; Yuhki, Yoshimitsu; Achiwa, Kazuto; Tadano, Kouji; Abe, Junko; Harada, Hiroshi; Hirano, Tetsuo

doi:10.5649/jjphcs.29.685

Cited by 2 publications

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“…The PD dose was also reduced within 6 months post‐transplant. The MMF dose was also reduced from 30 to 20 mg/kg, based on our experience that an MMF dose of more than 25 mg/kg resulted in high incidence of diarrhea (10). Early experiences with this regimen enabled rejection‐free courses during the first few months, and therefore we further began to reduce MMF dose between 10 and 15 mg/kg after 1 month post‐transplant.…”

Section: Discussionmentioning

confidence: 99%

Quadruple immunosuppression with basiliximab, tacrolimus, mycophenolate mofetil and prednisone is safe and effective for renal transplantation

Miura

Harada²,

Fukuzawa³

et al. 2005

Clinical Transplantation

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Section: Discussionmentioning

confidence: 99%

Quadruple immunosuppression with basiliximab, tacrolimus, mycophenolate mofetil and prednisone is safe and effective for renal transplantation

Miura

Harada²,

Fukuzawa³

et al. 2005

Clinical Transplantation

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“…Very recently, we investigated the frequency and severity of diarrhea between renal transplant recipients receiving MMF (MMF, prednisolone, and tacrolimus) and those not receiving MMF (azathioprine, prednisolone, and tacrolimus or CsA) in the immunosuppressive regimens at Sapporo City General Hospital. Statistical analysis revealed that diarrhea was more frequent and severe in the patients receiving MMF than in those not receiving it (Kobayashi et al, 2003). The frequency of diarrhea in the patients receiving MMF was approximately 74%.…”

mentioning

confidence: 91%

Cyclosporin A, but Not Tacrolimus, Inhibits the Biliary Excretion of Mycophenolic Acid Glucuronide Possibly Mediated by Multidrug Resistance-Associated Protein 2 in Rats

Kobayashi

Shinmoto²,

Kobayashi³

et al. 2004

J Pharmacol Exp Ther

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178

154

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The onset of diarrhea after the administration of mycophenolate mofetil (MMF) is possibly associated with the biliary excretion of its metabolite, mycophenolic acid glucuronide (MPAG). This study was undertaken to clarify the mechanism underlying the biliary excretion of MPAG. Intravenously administered mycophenolic acid (MPA, 5 mg/kg) rapidly disappeared from plasma and was efficiently excreted as MPAG in the bile of Wistar (26% of dose) and Sprague-Dawley rats (21% of dose) over 1 h. On the other hand, in spite of the rapid disappearance of MPA from plasma, the biliary excretion of MPAG was very limited in Eisai hyperbilirubinemic rats (EHBRs), which display mutations in multidrug resistance-associated protein 2 (Mrp2)/canalicular multispecific organic anion transporter, and constituted only 0.5% of dose. Instead, high levels of MPA were noted in the plasma of EHBRs. Intravenous administration of CsA (5 mg/kg) to Wistar rats significantly lowered the biliary excretion of MPAG. However, intravenously administered tacrolimus (0.1 mg/kg) failed to produce such effect. In conclusion, it is suggested that there is an efficient MPAG transport mediated by Mrp2 on the bile canalicular membrane of rat hepatocytes and that the therapeutic range of CsA potentially interferes with Mrp2. However, the therapeutic range of tacrolimus does not inhibit the transporter. Thus, it should be noted that MMF coadministered with tacrolimus instead of CsA might increase the occurrence of diarrhea related to the biliary excretion of MPAG in transplant recipients.

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Comparison of the Incidence of Diarrhea in Renal Transplant Patients with or without Mycophenolate Mofetil Administration

Cited by 2 publications

References 0 publications

Quadruple immunosuppression with basiliximab, tacrolimus, mycophenolate mofetil and prednisone is safe and effective for renal transplantation

Quadruple immunosuppression with basiliximab, tacrolimus, mycophenolate mofetil and prednisone is safe and effective for renal transplantation

Cyclosporin A, but Not Tacrolimus, Inhibits the Biliary Excretion of Mycophenolic Acid Glucuronide Possibly Mediated by Multidrug Resistance-Associated Protein 2 in Rats

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