Revival of effective and safe high-dose mizoribine for the kidney transplantation

Atsushi Sugitani, Hidehisa Kitada, Morihito Ota, Junichi Yoshida, Atsushi Doi, Hideki Hirakata, Masao Tanaka

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

We investigated whether high-dose Mizoribine (MIZ: a water-soluble anti-metabolite), 4-6 mg/kg/d was as effective and safe as mycophenolate mofetil (MMF) for patients after kidney transplantation. Between January 2001 and December 2005, 36 recipients at a stable phase more than one month passed after transplantation underwent conversion from MMF to MIZ, two from Azathioprine to MIZ, and two cases on MIZ from the beginning. There were 24-male and 16-female patients whose average age was 43.3 yr old and average weight was 54.0 kg. The types of transplantations were living donor renal transplantation 25, cadaveric renal transplantation 11, and simultaneous pancreas-kidney transplantation four examples. Of these, 33 patients were on Tacrolimus-based triple regimen and seven patients on Cyclosporine A base. The drugs used together with MIZ were basically the same as those before conversion. The reasons for conversion to MIZ were infection in 18 cases (45.0%), bone marrow suppression in nine cases (22.5%) and diarrhea in eight cases (20.0%), and post-transplant lymphoproliferative disorder in one case (2.5%). We initiated 4-6 mg/kg/d of MIZ divided twice a day depending on the serum creatinine (sCr) value of each patient. There was no big difference in the sCr value before and after MIZ administration in each individual patient, 1.79 ± 1.37 and 1.65 ± 1.30 mg/dL, respectively. A 12 h pharmaco-kinetic study of MIZ revealed that a peak value reached 2.87 μg/mL on average at three h (C3) followed by a slow decrease afterward. Acute rejection occurred in two cases and adverse effects were seen in five cases. The results of analysis of 349 points divided into three groups by renal function were as follows; poor renal function Group A revealed a trough level of 2.21 ± 0.99 μ g/mL and dosage 2.20 ± 1.06 mg/kg, good renal function Group B had a trough level of 1.06 ± 0.82 μg/mL and dosage 4.40 ± 1.72 mg/kg, and excellent function Group C had a trough level of 0.92 ± 0.55 μg/mL and dosage of 4.36 ± 1.08 mg/kg. High-dose MIZ 4-6 mg/kg/d is an anti-metabolite having an equivalent immunosuppressive effect, fewer serious adverse events and good cost-effectiveness as MMF even for patients with prolonged hemodialysis period and declined digestive function in Japan.

Original languageEnglish
Pages (from-to)590-595
Number of pages6
JournalClinical Transplantation
Volume20
Issue number5
DOIs
Publication statusPublished - Sep 1 2006

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Kidney Transplantation
Mycophenolic Acid
Kidney
Creatinine
Transplantation
Pancreas Transplantation
Lymphoproliferative Disorders
Living Donors
Azathioprine
Tacrolimus
Immunosuppressive Agents
bredinin
Serum
Cyclosporine
Cost-Benefit Analysis
Renal Dialysis
Diarrhea
Japan
Bone Marrow
Transplants

All Science Journal Classification (ASJC) codes

  • Transplantation

Cite this

Sugitani, A., Kitada, H., Ota, M., Yoshida, J., Doi, A., Hirakata, H., & Tanaka, M. (2006). Revival of effective and safe high-dose mizoribine for the kidney transplantation. Clinical Transplantation, 20(5), 590-595. https://doi.org/10.1111/j.1399-0012.2006.00522.x

Revival of effective and safe high-dose mizoribine for the kidney transplantation. / Sugitani, Atsushi; Kitada, Hidehisa; Ota, Morihito; Yoshida, Junichi; Doi, Atsushi; Hirakata, Hideki; Tanaka, Masao.

In: Clinical Transplantation, Vol. 20, No. 5, 01.09.2006, p. 590-595.

Research output: Contribution to journalArticle

Sugitani, A, Kitada, H, Ota, M, Yoshida, J, Doi, A, Hirakata, H & Tanaka, M 2006, 'Revival of effective and safe high-dose mizoribine for the kidney transplantation', Clinical Transplantation, vol. 20, no. 5, pp. 590-595. https://doi.org/10.1111/j.1399-0012.2006.00522.x
Sugitani, Atsushi ; Kitada, Hidehisa ; Ota, Morihito ; Yoshida, Junichi ; Doi, Atsushi ; Hirakata, Hideki ; Tanaka, Masao. / Revival of effective and safe high-dose mizoribine for the kidney transplantation. In: Clinical Transplantation. 2006 ; Vol. 20, No. 5. pp. 590-595.
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