Effect of single-dose oral mizoribine pulse therapy twice per week for frequently relapsing steroid-dependent nephrotic syndrome.
OBJECTIVE
To evaluate the efficacy of single-dose oral mizoribine (MZB) pulse therapy given twice weekly for frequently relapsing steroid-dependent nephrotic syndrome (FR-SDNS).


METHODS
The subjects were 8 patients with FR-SDNS with a median age of 6.9 years old (range 3.1 - 18.0 y). The study was performed as a Phase II trial. The MZB dose was adjusted to achieve a peak blood level of 3 - 5 μg/ml (3.9 - 15.9 mg/kg/d, maximum dose: 750 mg) using a single dose given twice weekly before a meal. The therapeutic benefits of MZB pulse therapy were assessed based on a comparison of the incidence of relapse and the required daily dosage of prednisolone (PSL) in the 12 months prior to and following therapy.


RESULTS
The incidence of relapse after therapy was significantly lower than that before therapy (2.5 ± 1.4 vs. 4.3 ± 0.5, p < 0.01) and the required daily dosage of prednisolone (PSL) after therapy was lower than that before therapy (0.48 ± 0.23 vs. 0.52 ± 0.32 mg/kg/d, not significant). However, this therapy was not effective for 3 out of 4 patients treated with cyclosporine. During follow-up, discontinuation of PSL was possible in 4 of 5 patients who showed a decreased rate of relapse after therapy. The peak blood concentration of MZB in these patients was significantly higher than that in 3 patients who did not show a decreased rate of relapse (3.95 ± 0.11 vs. 3.05 ± 0.21 μg/ml, p < 0.01). No adverse effects were observed in any patients.


CONCLUSIONS
Our results show that single-dose oral MZB pulse therapy is effective in decreasing the frequency of relapse in some pediatric patients with FR-SDNS. A peak concentration of MZB of ~3.8 - 4.0 μg/ ml may be required for FR-SDNS therapy.
Department of Pediatrics, Kochi Medical School, Kochi University, Kochi, Japan. fujiedam@kochi-u.ac.jp
Mikiya
M
Fujieda
Masayuki
M
Ishihara
Taku
T
Morita
Atsushi
A
Hayashi
Shinichi
S
Okada
Toshiyuki
T
Ohta
Takashi
T
Sakano
Hiroshi
H
Wakiguchi
D000284:Administration, Oral; D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D016572:Cyclosporine / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D007223:Infant; D007564:Japan; D008297:Male; D009404:Nephrotic Syndrome / Q000188:drug therapy*; D011239:Prednisolone / Q000008:administration & dosage*; D020551:Pulse Therapy, Drug; D012008:Recurrence; D012263:Ribonucleosides / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D013256:Steroids / Q000008:administration & dosage*; D013997:Time Factors; D016896:Treatment Outcome
D007166:Immunosuppressive Agents; D012263:Ribonucleosides; D013256:Steroids; C010052:mizoribine; D016572:Cyclosporine; D011239:Prednisolone