Population pharmacokinetics and initial dose optimization of tacrolimus in children with severe combined immunodeficiency undergoing hematopoietic stem cell transplantation

Chen, Xiao; Wang, Dongdong; Zheng, Feng; Zhai, Xiaowen; Xu, Hong; Li, Zhiping

doi:10.3389/fphar.2022.869939

Cited by 2 publications

References 31 publications

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External evaluation of a population pharmacokinetic model of tacrolimus after hematopoietic stem cell transplantation in children with thalassemia

Niu,

Qi,

et al. 2023

Preprint

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Objective Tacrolimus (TAC), a narrow therapeutic window drug, several population pharmacokinetic (PopPK) models of TAC have been established to explore its optimized treatment regimen after hematopoietic stem cell transplantation (HSCT). However, there is no evidence of the predictive performance of these models when extrapolated to different clinical centers. We aimed to perform a systematic external evaluation of the published TAC PopPK models and to identify underlying influence elements. Methods Published population pharmacokinetic models of oral TAC after HSCT were searched for external assessment using TAC blood trough concentrations of pediatrics with β-thalassemia major (β-TM) after HSCT at the First Affiliated Hospital of Guangxi Medical University. The effect of prior information on model predictability was determined by Prediction error (PE%)、Visual predictive check (VPC)、Normalized prediction distribution error (NPDE) test and Bayesian prediction. Results Two published population pharmacokinetic models were evaluated by including 296 oral TAC blood concentrations from 46 children. Evaluation results on the basis of prediction errors, simulations, and Bayesian founded that population of published model may affect the transferability of the model. TAC bioassay methods in different centers may also result in an undesirable predictive performance of model extrapolation. Conclusion Individualized dosing with frequent therapeutic drug monitoring during the use of TAC was confirmed to be of clinical value. The two published models of oral TAC after HSCT have performed unsatisfactorily in all aspects of predictive diagnostics and are therefore not suitable for direct extrapolation to use in children with β-TM in our center.

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External evaluation of a population pharmacokinetic model of tacrolimus after hematopoietic stem cell transplantation in children with thalassemia

Niu,

Qi,

et al. 2023

Preprint

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

Han,

Rui,

Yang

et al. 2024

CPD

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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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Population pharmacokinetics and initial dose optimization of tacrolimus in children with severe combined immunodeficiency undergoing hematopoietic stem cell transplantation

Cited by 2 publications

References 31 publications

External evaluation of a population pharmacokinetic model of tacrolimus after hematopoietic stem cell transplantation in children with thalassemia

External evaluation of a population pharmacokinetic model of tacrolimus after hematopoietic stem cell transplantation in children with thalassemia

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

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