What is the reason why does mizoribine ineffectiveness for the patient with steroid―resistant nephrotic syndrome?

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We report the case of a 3―year―old female patient with steroid―resistant nephrotic syndrome. Although mizoribine (MZR) was administered at a dose of 9.5 mg/kg body weight/day, the peak MZR serum concentration (Cmax) was 1.07 μg/ml, which was low and clinically inefficacious. By the investigation of this issue, it was revealed that the apparent volume of distribution (Vd/F) was extremely high (5.97l/kg), the urinary excretion rate of MZR (fu) was low (17.4%), and the absolute volume of distribution (Vd) was 1.04l/kg, which value was consistent with that of a water―soluble drug. Hence, the reason for the low Cmax was the decreased absorption of MZR. The fu of MZR is considered to indicate the bioavailability or absorption rate of MZR. When fu is low, an extremely high Vd/F will be obtained. If Vd/F is high or Cmax or fu is low, the decreased absorption of MZR might result in an insufficient concentration of MZR in serum even after the administration of a high dose of MZR.