title: Mizoribine therapy combined with steroids and mizoribine blood concentration monitoring for idiopathic membranous nephropathy with steroid-resistant nephrotic syndrome.
abstract: BACKGROUND
  We designed a prospective and randomized trial of mizoribine (MZR) therapy combined with prednisolone (PSL) for idiopathic membranous nephropathy (IMN) with steroid-resistant nephrotic syndrome (SRNS).
  
  
  METHODS
  Patients with IMN were divided into 2 groups, and MZR combined with PSL was administered for 2 years. PSL was initially prescribed at 40 mg/day and tapered. MZR was given once-a-day at 150 mg and 3-times-a-day at 50 mg each to groups 1 and 2. Serum MZR concentrations from 0 to 4 h after administration were examined within one month of treatment. The concentration curve and peak serum level (Cmax) of MZR were estimated by the population pharmacokinetic (PPK) parameters of MZR.
  
  
  RESULTS
  At 2 years, 10 of 19 patients (52.6 %) in group 1 and 7 of 18 patients (38.9 %) in group 2 achieved complete remission (CR). The time-to-remission curve using the Kaplan-Meier technique revealed an increase in the cumulative CR rate in group 1, but no significant difference between the groups. Meanwhile, there was a significant difference in Cmaxbetween groups 1 and 2 (mean ± SD: 1.20 ± 0.52 vs. 0.76 ± 0.39 μg/mL, p = 0.04), and Cmaxlevels in CR cases were significantly higher than those in non-CR cases. Receiver operating characteristic analysis showed that Cmaxmore than 1.1 µg/mL was necessary for CR in once-a-day administration.
  
  
  CONCLUSIONS
  Administration of MZR once a day is useful when combined with PSL for treatment of IMN with SRNS. In addition, it is important to assay the serum concentration of MZR and to determine Cmax, and more than 1.1 µg/mL of Cmaxis necessary for CR.
authors: Professor Emeritus, Fukuoka University, and Sanko Clinic, 4-9-3 Ropponmatsu, Chuo-ku, Fukuoka, 810-0044, Japan. tsaito@fukuoka-u.ac.jp.
authors: Takao
authors: http://orcid.org/0000-0002-1279-6400
authors: T
authors: Saito
authors: Division of Nephrology, Department of General Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, Japan.
authors: Masayuki
authors: M
authors: Iwano
authors: The University Research Center, General Science Institute, School of Medicine, Nihon University, Tokyo, Japan.
authors: Koichi
authors: K
authors: Matsumoto
authors: Department of Nephrology and Blood Purification, Saitama Medical Center, Saitama Medical University, Kawagoe, Japan.
authors: Tetsuya
authors: T
authors: Mitarai
authors: Division of Nephrology, Kanazawa Medical University School of Medicine, Ishikawa, Japan.
authors: Hitoshi
authors: H
authors: Yokoyama
authors: Hiroshima Kidney Organization, Hiroshima, Japan.
authors: Noriaki
authors: N
authors: Yorioka
authors: Division of Nephrology and Kidney Center, Kobe University Graduate School of Medicine, Kobe, Japan.
authors: Shinichi
authors: S
authors: Nishi
authors: Division of Nephrology, Department of Internal Medicine, Showa University Fujigaoka Hospital, Yokohama, Japan.
authors: Ashio
authors: A
authors: Yoshimura
authors: Division of Nephrology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors: Hiroshi
authors: H
authors: Sato
authors: Division of Nephrology and Rheumatology, Faculty of Medicine, Fukuoka University, Fukuoka, Japan.
authors: Satoru
authors: S
authors: Ogahara
authors: Division of Nephrology and Rheumatology, Faculty of Medicine, Fukuoka University, Fukuoka, Japan.
authors: Yoshie
authors: Y
authors: Sasatomi
authors: Department of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan.
authors: Yasufumi
authors: Y
authors: Kataoka
authors: Ueda Clinic, Chiba, Japan.
authors: Shiro
authors: S
authors: Ueda
authors: Professor Emeritus, Tsukuba University, Ibaraki, Japan.
authors: Akio
authors: A
authors: Koyama
authors: Department of Nephrology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors: Shoichi
authors: S
authors: Maruyama
authors: Division of Nephrology and Endocrinology, University of Tokyo School of Medicine, Tokyo, Japan.
authors: Masaomi
authors: M
authors: Nangaku
authors: Nakayamadera Imai Clinic, Hyogo, Japan.
authors: Enyu
authors: E
authors: Imai
authors: Department of Nephrology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors: Seiichi
authors: S
authors: Matsuo
authors: Professor Emeritus, Juntendo University, Tokyo, Japan.
authors: Yasuhiko
authors: Y
authors: Tomino
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D015433:Glomerulonephritis, Membranous / Q000150:complications / Q000188:drug therapy*; D005938:Glucocorticoids / Q000008:administration & dosage; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D008297:Male; D008875:Middle Aged; D009404:Nephrotic Syndrome / Q000188:drug therapy* / Q000209:etiology; D011239:Prednisolone / Q000008:administration & dosage; D011446:Prospective Studies; D012263:Ribonucleosides / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics
chemical_list: D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D012263:Ribonucleosides; C010052:mizoribine; D011239:Prednisolone
keywords: Estimated serum concentration curve; Idiopathic membranous nephropathy; Mizoribine; Once-a-day administration; Steroid-resistant nephrotic syndrome