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Initial dose recommendation for sirolimus in paediatric kaposiform haemangioendothelioma patients based on population pharmacokinetics and pharmacogenomics

OBJECTIVE: Sirolimus has been used to treat paediatric kaposiform haemangioendothelioma patients. However, there is considerable pharmacokinetic variability among individuals, and it is difficult to develop an initial dosing regimen. The goal of the present study is to recommend an initial sirolimus...

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Autores principales: Chen, Xiao, Wang, Dong-Dong, Xu, Hong, Li, Zhi-Ping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: SAGE Publications 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7444137/
https://www.ncbi.nlm.nih.gov/pubmed/32815764
http://dx.doi.org/10.1177/0300060520947627
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author Chen, Xiao
Wang, Dong-Dong
Xu, Hong
Li, Zhi-Ping
author_facet Chen, Xiao
Wang, Dong-Dong
Xu, Hong
Li, Zhi-Ping
author_sort Chen, Xiao
collection PubMed
description OBJECTIVE: Sirolimus has been used to treat paediatric kaposiform haemangioendothelioma patients. However, there is considerable pharmacokinetic variability among individuals, and it is difficult to develop an initial dosing regimen. The goal of the present study is to recommend an initial sirolimus dose in paediatric kaposiform haemangioendothelioma patients based on population pharmacokinetics and pharmacogenomics. METHODS: This was a retrospective clinical study. A population pharmacokinetics model was established and population characteristics, laboratory test results, drug combinations, and pharmacogenomics were considered as potential covariates. The Monte Carlo method was used to simulate the optimal initial dosage. RESULTS: The final covariates that affect sirolimus clearance include weight and the CYP3A5 genotype. The initial dosage of sirolimus for individuals with CYP3A5*3/*3 was 0.20 mg/kg split into two doses for 5 to 60 kg body weight. For individuals with CYP3A5*1, the initial dose was 0.23 mg/kg split into two doses for 5 to 30 kg body weight and 0.20 mg/kg split into two doses for 30 to 60 kg body weight. CONCLUSION: The recommendation for the initial sirolimus dose in paediatric kaposiform haemangioendothelioma patients was based on population pharmacokinetics and pharmacogenomics. This study may provide practical value for sirolimus clinical use in paediatric kaposiform haemangioendothelioma patients.
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spelling pubmed-74441372020-09-09 Initial dose recommendation for sirolimus in paediatric kaposiform haemangioendothelioma patients based on population pharmacokinetics and pharmacogenomics Chen, Xiao Wang, Dong-Dong Xu, Hong Li, Zhi-Ping J Int Med Res Retrospective Clinical Research Report OBJECTIVE: Sirolimus has been used to treat paediatric kaposiform haemangioendothelioma patients. However, there is considerable pharmacokinetic variability among individuals, and it is difficult to develop an initial dosing regimen. The goal of the present study is to recommend an initial sirolimus dose in paediatric kaposiform haemangioendothelioma patients based on population pharmacokinetics and pharmacogenomics. METHODS: This was a retrospective clinical study. A population pharmacokinetics model was established and population characteristics, laboratory test results, drug combinations, and pharmacogenomics were considered as potential covariates. The Monte Carlo method was used to simulate the optimal initial dosage. RESULTS: The final covariates that affect sirolimus clearance include weight and the CYP3A5 genotype. The initial dosage of sirolimus for individuals with CYP3A5*3/*3 was 0.20 mg/kg split into two doses for 5 to 60 kg body weight. For individuals with CYP3A5*1, the initial dose was 0.23 mg/kg split into two doses for 5 to 30 kg body weight and 0.20 mg/kg split into two doses for 30 to 60 kg body weight. CONCLUSION: The recommendation for the initial sirolimus dose in paediatric kaposiform haemangioendothelioma patients was based on population pharmacokinetics and pharmacogenomics. This study may provide practical value for sirolimus clinical use in paediatric kaposiform haemangioendothelioma patients. SAGE Publications 2020-08-20 /pmc/articles/PMC7444137/ /pubmed/32815764 http://dx.doi.org/10.1177/0300060520947627 Text en © The Author(s) 2020 https://creativecommons.org/licenses/by-nc/4.0/ Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).
spellingShingle Retrospective Clinical Research Report
Chen, Xiao
Wang, Dong-Dong
Xu, Hong
Li, Zhi-Ping
Initial dose recommendation for sirolimus in paediatric kaposiform haemangioendothelioma patients based on population pharmacokinetics and pharmacogenomics
title Initial dose recommendation for sirolimus in paediatric kaposiform haemangioendothelioma patients based on population pharmacokinetics and pharmacogenomics
title_full Initial dose recommendation for sirolimus in paediatric kaposiform haemangioendothelioma patients based on population pharmacokinetics and pharmacogenomics
title_fullStr Initial dose recommendation for sirolimus in paediatric kaposiform haemangioendothelioma patients based on population pharmacokinetics and pharmacogenomics
title_full_unstemmed Initial dose recommendation for sirolimus in paediatric kaposiform haemangioendothelioma patients based on population pharmacokinetics and pharmacogenomics
title_short Initial dose recommendation for sirolimus in paediatric kaposiform haemangioendothelioma patients based on population pharmacokinetics and pharmacogenomics
title_sort initial dose recommendation for sirolimus in paediatric kaposiform haemangioendothelioma patients based on population pharmacokinetics and pharmacogenomics
topic Retrospective Clinical Research Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7444137/
https://www.ncbi.nlm.nih.gov/pubmed/32815764
http://dx.doi.org/10.1177/0300060520947627
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