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ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

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Research Article

The Impact of Spironolactone Co-administration on Cyclosporin Initial Dosage Optimization for Pediatric Refractory Nephrotic Syndrome

Author(s): Huan-Huan Han, Min Rui, Yang Yang*, Jia-Fang Cui, Xue-Ting Huang, Shi-Jia Zhang, Su-Mei He, Dong-Dong Wang* and Xiao Chen*

Volume 30, Issue 18, 2024

Published on: 18 April, 2024

Page: [1419 - 1432] Pages: 14

DOI: 10.2174/0113816128307797240416053723

Price: $65

Abstract

Objectives: Cyclosporin has been used for the treatment of pediatric refractory nephrotic syndrome (PRNS). However, the narrow therapeutic window and large pharmacokinetic variability make it difficult to individualize cyclosporin administration. Meanwhile, spironolactone has been reported to affect cyclosporin metabolism in PRNS patients. This study aims to explore the initial dosage optimization of cyclosporin in PRNS based on the impact of spironolactone co-administration.

Methods: Monte Carlo simulation based on a previously established cyclosporin population pharmacokinetic model for PRNS was used to design cyclosporin dosing regimen.

Results: In this study, the probability of drug concentration reaching the target and the convenience of times of administration were considered comprehensively. The optimal administration regimen in PRNS without spironolactone was 6, 5, 4 and 3 mg/kg cyclosporin split into two doses for the body weight of 5-8, 8-18, 18-46 and 46-70 kg, respectively. The optimal administration regimen in PRNS with spironolactone was 4, 3, 2 mg/kg cyclosporin split into two doses for body weight of 5-14, 14-65, and 65-70 kg, respectively.

Conclusion: The cyclosporin dosing regimen for PRNS based on Monte Carlo simulation was systematically developed and the initial dosage optimization of cyclosporin in PRNS was recommended for the first time.

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