Association of Cumulative Cyclosporine Dose with Its Irreversible Nephrotoxicity in Japanese Patients with Pediatric-Onset Autoimmune Diseases

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Author(s)

Abstract

Cyclosporine (CsA)-induced nephrotoxicity can become a major obstacle to continuous use. The aim of this study was to optimize CsA dose to avoid its irreversible nephrotoxicity. Twenty-three Japanese patients with pediatric-onset systemic lupus erythematosus or idiopathic nephrotic syndrome, who were maintained in a stable condition by oral dosing of CsA microemulsion, were enrolled in this study. The patients were stratified into 3 groups; those with no, reversible, and irreversible nephrotoxicity, according to periodically performed renal pathohistological examinations. A higher concentration of CsA in blood (<i>p</i>=0.002—0.011) and a longer duration of CsA treatment (<i>p</i>=0.002) were risk factors for irreversible nephrotoxicity, and the cumulative CsA dose, the product of the maintenance dose and duration of CsA treatment, was predictive of nephrotoxicity (<i>p</i>=0.036). The maximum target blood concentration at 2 h post-dose, C<sub>2</sub>, to avoid CsA-induced irreversible nephrotoxicity was 700 ng/ml, although the cumulative CsA dose of 4850 mg/kg would result in a 50% probability of nephrotoxicity.

Journal

  • Biological and Pharmaceutical Bulletin

    Biological and Pharmaceutical Bulletin 30(12), 2371-2375, 2007-12-01

    The Pharmaceutical Society of Japan

References:  30

Cited by:  1

Codes

  • NII Article ID (NAID)
    110006546441
  • NII NACSIS-CAT ID (NCID)
    AA10885497
  • Text Lang
    ENG
  • Article Type
    Journal Article
  • ISSN
    09186158
  • NDL Article ID
    9274639
  • NDL Source Classification
    ZS51(科学技術--薬学)
  • NDL Call No.
    Z53-V41
  • Data Source
    CJP  CJPref  NDL  NII-ELS  J-STAGE 
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