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Biol Pharm Bull. 2007 Dec;30(12):2371-5.

Association of cumulative cyclosporine dose with its irreversible nephrotoxicity in Japanese patients with pediatric-onset autoimmune diseases.

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1
Department of Hospital Pharmacy, Kobe University School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.

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, C(2), 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.

PMID:
18057728
DOI:
10.1248/bpb.30.2371
[Indexed for MEDLINE]
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