Biological and Pharmaceutical Bulletin
Online ISSN : 1347-5215
Print ISSN : 0918-6158
ISSN-L : 0918-6158
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Association of Cumulative Cyclosporine Dose with Its Irreversible Nephrotoxicity in Japanese Patients with Pediatric-Onset Autoimmune Diseases
Tsutomu NakamuraKandai NozuKazumoto IijimaNorishige YoshikawaYuka MoriyaMotohiro YamamoriAsae KakoMasafumi MatsuoAki SakuraiNoboru OkamuraToshihisa IshikawaKatsuhiko OkumuraToshiyuki Sakaeda
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2007 Volume 30 Issue 12 Pages 2371-2375

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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 (p=0.002—0.011) and a longer duration of CsA treatment (p=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 (p=0.036). The maximum target blood concentration at 2 h post-dose, C2, 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.

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© 2007 The Pharmaceutical Society of Japan
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