Title:The Impact of Spironolactone Co-administration on Cyclosporin Initial Dosage
Optimization for Pediatric Refractory Nephrotic Syndrome
Volume: 30
Issue: 18
Author(s): Huan-Huan Han, Min Rui, Yang Yang*, Jia-Fang Cui, Xue-Ting Huang, Shi-Jia Zhang, Su-Mei He, Dong-Dong Wang*Xiao Chen*
Affiliation:
- Department of Pharmacy, The Affiliated Changzhou Children’s Hospital of Nantong University, Changzhou,
Jiangsu 213003, China
- Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, School of Pharmacy, Xuzhou Medical
University, Xuzhou, Jiangsu 221004, China
- School of Nursing, Xuzhou Medical University, Xuzhou, Jiangsu 221004,
China
Keywords:
Cyclosporin, dosing proposal, spironolactone, pediatric refractory nephrotic syndrome, Monte Carlo simulation, population pharmacokinetic model.
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.
