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

  • Authors: Han H.1, Rui M.2, Yang Y.3, Cui J.4, Huang X.4, Zhang S.5, He S.6, Wang D.4, Chen X.7
  • Affiliations:
    1. Department of Pharmacy, The Affiliated Lianyungang Hospital of Xuzhou Medical University
    2. Department of Orthopaedics, The Affiliated Jiangyin Clinical College of Xuzhou Medical University
    3. Department of Pharmacy, The Affiliated Changzhou Children’s Hospital of Nantong University
    4. Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, School of Pharmacy,, Xuzhou Medical University
    5. Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, School of Pharmacy, Xuzhou Medical University
    6. Department of Pharmacy, Suzhou Hospital, Affiliated Hospital of Medical School,, Nanjing University
    7. School of Nursing, Xuzhou Medical University
  • Issue: Vol 30, No 18 (2024)
  • Pages: 1419-1432
  • Section: Immunology, Inflammation & Allergy
  • URL: https://rjsvd.com/1381-6128/article/view/645718
  • DOI: https://doi.org/10.2174/0113816128307797240416053723
  • ID: 645718

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Full Text

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.

About the authors

Huan-Huan Han

Department of Pharmacy, The Affiliated Lianyungang Hospital of Xuzhou Medical University

Email: info@benthamscience.net

Min Rui

Department of Orthopaedics, The Affiliated Jiangyin Clinical College of Xuzhou Medical University

Email: info@benthamscience.net

Yang Yang

Department of Pharmacy, The Affiliated Changzhou Children’s Hospital of Nantong University

Author for correspondence.
Email: info@benthamscience.net

Jia-Fang Cui

Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, School of Pharmacy,, Xuzhou Medical University

Email: info@benthamscience.net

Xue-Ting Huang

Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, School of Pharmacy,, Xuzhou Medical University

Email: info@benthamscience.net

Shi-Jia Zhang

Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, School of Pharmacy, Xuzhou Medical University

Email: info@benthamscience.net

Su-Mei He

Department of Pharmacy, Suzhou Hospital, Affiliated Hospital of Medical School,, Nanjing University

Email: info@benthamscience.net

Dong-Dong Wang

Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, School of Pharmacy,, Xuzhou Medical University

Author for correspondence.
Email: info@benthamscience.net

Xiao Chen

School of Nursing, Xuzhou Medical University

Author for correspondence.
Email: info@benthamscience.net

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