title: Efficacy of weekly mizoribine pulse therapy in refractory lupus nephritis.
abstract: OBJECTIVE
  We investigated the efficacy of a high-dose intermittent dosing treatment method (weekly mizoribine pulse therapy) conceived in the hope of achieving better efficacy by increasing the peak blood levels of mizoribine in patients with refractory lupus nephritis.
  
  
  METHODS
  Seventeen patients with lupus nephritis who had been resistant to corticosteroid and immunosuppressant therapy received weekly mizoribine pulse therapy. Mizoribine (350 mg) was administered three times at 12 h intervals over 2 consecutive days (700 mg for day 1 and 350 mg for day 2), followed by a washout period from day 3 to day 7.
  
  
  RESULTS
  This therapeutic strategy enabled the peak blood levels of mizoribine to be increased to more than 3 μg/mL in most of the patients. Although SLEDAI, anti-ds-DNA antibody titer, CH-50, and serum albumin level did not significantly improve, urinary protein levels decreased, and it was possible to taper the dose of concomitant steroids. Using our definition of clinical response, 10 of the 17 patients were responders and 4 of them were nonresponders. The average peak serum mizoribine concentration of the responders was as high as 3.5 μg/mL. Elevation of serum liver enzymes was seen in 1 patient, and hyperuricemia occurred in 4 cases, but none of these adverse events were serious.
  
  
  CONCLUSIONS
  Intermittent administration of mizoribine can increase blood levels and may be effective for refractory lupus nephritis.
authors.affiliation: Department of Rheumatology and Clinical Immunology, Saitama Medical Center, Saitama Medical University, 1981 Kamoda, Kawagoe, Saitama, 350-8550, Japan.
authors.forename: Eiko
authors.initials: E
authors.lastname: Nishi
authors.forename: Hideto
authors.initials: H
authors.lastname: Kameda
authors.forename: Hiroe
authors.initials: H
authors.lastname: Ogawa
authors.forename: Hayato
authors.initials: H
authors.lastname: Nagasawa
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Takei
authors.forename: Ayumi
authors.initials: A
authors.lastname: Okuyama
authors.forename: Takahiko
authors.initials: T
authors.lastname: Kurasawa
authors.forename: Tsuneo
authors.initials: T
authors.lastname: Kondo
authors.forename: Koji
authors.initials: K
authors.lastname: Nishimura
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Shirai
authors.forename: Ryota
authors.initials: R
authors.lastname: Sakai
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Ito
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Takeuchi
authors.forename: Koichi
authors.initials: K
authors.lastname: Amano
mesh_terms: D000293:Adolescent; D000328:Adult; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004351:Drug Resistance; D057915:Drug Substitution; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008181:Lupus Nephritis / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D020551:Pulse Therapy, Drug; D012263:Ribonucleosides / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D012720:Severity of Illness Index; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; D012263:Ribonucleosides; C010052:mizoribine