Title:The Dosage Recommendation of Cyclosporin in Children with Hemophagocytic
Lymphohistiocytosis based on Population Pharmacokinetic Model
Volume: 29
Issue: 37
Author(s): Yang Yang, Ya-Feng Li, Ke Hu, Shi-Jia Zhang, Jia-Fang Cui, Xue-Ting Huang, Su-Mei He*, Dong-Dong Wang*Xiao Chen*
Affiliation:
- Department
of Pharmacy, Suzhou Hospital, Affiliated Hospital of Medical School, Nanjing University, Suzhou, Jiangsu 215153, 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:
Cyclosporine, dosage recommendation, pediatric hemophagocytic lymphohistiocytosis, piperacillin-tazobactam, Monte Carlo simulation, pharmacokinetic model.
Abstract:
Objectives: Cyclosporin is one of the therapeutic regimens for hemophagocytic lymphohistiocytosis
(HLH); however, the optimal dosage of cyclosporine in children with HLH is unknown. It has been found that
piperacillin-tazobactam affects the cyclosporine pharmacokinetic process in pediatric HLH patients. Thus, the
purpose of the present study was to recommend cyclosporin dosage for pediatric HLH with and without piperacillin-
tazobactam.
Methods: A previously established cyclosporine population pharmacokinetic model for pediatric HLH patients
has been used in this study to recommend optimal dosage based on Monte Carlo simulation. The pediatric
HLH patients have been included in eight weight groups (5, 10, 20, 30, 40, 50, 60, 70 kg) for sixteen
dosages (1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16 mg/kg), split into one dose or two doses.
Results: The optimal cyclosporin dosages for children having HLH without piperacillin-tazobactam have been
found to be 15, 13, 12, 11, 10, and 9 mg/kg, split into two doses for weights of 5-7, 7-10, 10-20, 20-28, 28-45,
and 45-70 kg, respectively. For children with HLH, optimal cyclosporin dosages with piperacillin-tazobactam
have been found to be 8 and 7 mg/kg, split into two doses for weights of 5-20 and 20-70 kg, respectively.
Conclusion: It is the first time that the cyclosporin dosage regimens for HLH in children have been developed
based on Monte Carlo simulation, and the initial dosage optimizations of cyclosporine in pediatric HLH patients
have been recommended.