Revival of effective and safe high-dose mizoribine for the kidney transplantation.
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 microg/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 microg/mL and dosage 2.20 +/- 1.06 mg/kg, good renal function Group B had a trough level of 1.06 +/- 0.82 microg/mL and dosage 4.40 +/- 1.72 mg/kg, and excellent function Group C had a trough level of 0.92 +/- 0.55 microg/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.
Sugitani
Atsushi
A
Kidney Care Unit, Department of Surgery and Oncology, Kyushu University, Fukuoka, Japan. sugitani@surg1.med.kyushu-u.ac.jp
Kitada
Hidehisa
H
Ota
Morihito
M
Yoshida
Junichi
J
Doi
Atsushi
A
Hirakata
Hideki
H
Tanaka
Masao
M
D000293:Adolescent; D000328:Adult; D000963:Antimetabolites / Q000008:administration & dosage* / Q000009:adverse effects; D001379:Azathioprine / Q000008:administration & dosage; D005260:Female; D006084:Graft Rejection; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives; D016035:Pancreas Transplantation; D012263:Ribonucleosides / Q000008:administration & dosage* / Q000009:adverse effects; D016559:Tacrolimus / Q000008:administration & dosage
D000963:Antimetabolites; D007166:Immunosuppressive Agents; D012263:Ribonucleosides; C010052:mizoribine; D009173:Mycophenolic Acid; D001379:Azathioprine; D016559:Tacrolimus