{"title":"在接受造血干细胞移植的泰国儿科患者中,根据模型对静脉注射布舒凡进行精确配药。","authors":"Apichaya Puangpetch, Fabienne Thomas, Usanarat Anurathapan, Samart Pakakasama, Suradej Hongeng, Jiratha Rachanakul, Santirhat Prommas, Nutthan Nuntharadthanaphong, Étienne Chatelut, Chonlaphat Sukasem, Félicien Le Louedec","doi":"10.1097/FTD.0000000000001225","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Conditioning bifunctional agent, busulfan, is commonly used on children before hematopoietic stem cell transplantation. Currently, at the Ramathibodi hospital, Bangkok, Thailand, initial dosing is calculated according to age and body surface area, and 7 samples per day are used for therapeutic drug monitoring (TDM). This study aimed to identify the best strategies for individual dosages a priori from patient characteristics and a posteriori based on TDM.</p><p><strong>Methods: </strong>The pharmacokinetic data set consisted of 2018 plasma concentrations measured in 135 Thai (n = 135) pediatric patients (median age = 8 years) and were analyzed using a population approach.</p><p><strong>Results: </strong>Body weight, presence of malignant disease, and genetic polymorphism of Glutathione S-transferase Alpha-1 (GSTA1) were predictors of clearance. The optimum sampling times for TDM concentration measurements were 0.25, 2, and 5 hours after a 3-hour infusion. This was sufficient to obtain a Bayesian estimate of clearance a posteriori. Simulations showed the poor performance of a priori formula-based dose calculations with 90% of patients demonstrating a 69%-151% exposure interval around the target. This interval shrank to 85%-124% if TDM was carried out only at day 1 and to 90%-116% with TDM at days 1 and 3.</p><p><strong>Conclusions: </strong>This comprehensive study reinforces the interest of TDM in managing interindividual variability in busulfan exposure. Therapeutic drug monitoring can reliably be implemented from 3 samples using the Bayesian approach, preferably over 2 days. If using the latter is not possible, the formulas developed herein could present an alternative in Thai patients.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":null,"pages":null},"PeriodicalIF":2.8000,"publicationDate":"2024-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Model-Informed Precision Dosing of Intravenous Busulfan in Thai Pediatrics Undergoing Hematopoietic Stem Cell Transplantation.\",\"authors\":\"Apichaya Puangpetch, Fabienne Thomas, Usanarat Anurathapan, Samart Pakakasama, Suradej Hongeng, Jiratha Rachanakul, Santirhat Prommas, Nutthan Nuntharadthanaphong, Étienne Chatelut, Chonlaphat Sukasem, Félicien Le Louedec\",\"doi\":\"10.1097/FTD.0000000000001225\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Conditioning bifunctional agent, busulfan, is commonly used on children before hematopoietic stem cell transplantation. Currently, at the Ramathibodi hospital, Bangkok, Thailand, initial dosing is calculated according to age and body surface area, and 7 samples per day are used for therapeutic drug monitoring (TDM). This study aimed to identify the best strategies for individual dosages a priori from patient characteristics and a posteriori based on TDM.</p><p><strong>Methods: </strong>The pharmacokinetic data set consisted of 2018 plasma concentrations measured in 135 Thai (n = 135) pediatric patients (median age = 8 years) and were analyzed using a population approach.</p><p><strong>Results: </strong>Body weight, presence of malignant disease, and genetic polymorphism of Glutathione S-transferase Alpha-1 (GSTA1) were predictors of clearance. The optimum sampling times for TDM concentration measurements were 0.25, 2, and 5 hours after a 3-hour infusion. This was sufficient to obtain a Bayesian estimate of clearance a posteriori. Simulations showed the poor performance of a priori formula-based dose calculations with 90% of patients demonstrating a 69%-151% exposure interval around the target. This interval shrank to 85%-124% if TDM was carried out only at day 1 and to 90%-116% with TDM at days 1 and 3.</p><p><strong>Conclusions: </strong>This comprehensive study reinforces the interest of TDM in managing interindividual variability in busulfan exposure. Therapeutic drug monitoring can reliably be implemented from 3 samples using the Bayesian approach, preferably over 2 days. If using the latter is not possible, the formulas developed herein could present an alternative in Thai patients.</p>\",\"PeriodicalId\":23052,\"journal\":{\"name\":\"Therapeutic Drug Monitoring\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.8000,\"publicationDate\":\"2024-05-14\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Therapeutic Drug Monitoring\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1097/FTD.0000000000001225\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"MEDICAL LABORATORY TECHNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Therapeutic Drug Monitoring","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1097/FTD.0000000000001225","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"MEDICAL LABORATORY TECHNOLOGY","Score":null,"Total":0}
Model-Informed Precision Dosing of Intravenous Busulfan in Thai Pediatrics Undergoing Hematopoietic Stem Cell Transplantation.
Background: Conditioning bifunctional agent, busulfan, is commonly used on children before hematopoietic stem cell transplantation. Currently, at the Ramathibodi hospital, Bangkok, Thailand, initial dosing is calculated according to age and body surface area, and 7 samples per day are used for therapeutic drug monitoring (TDM). This study aimed to identify the best strategies for individual dosages a priori from patient characteristics and a posteriori based on TDM.
Methods: The pharmacokinetic data set consisted of 2018 plasma concentrations measured in 135 Thai (n = 135) pediatric patients (median age = 8 years) and were analyzed using a population approach.
Results: Body weight, presence of malignant disease, and genetic polymorphism of Glutathione S-transferase Alpha-1 (GSTA1) were predictors of clearance. The optimum sampling times for TDM concentration measurements were 0.25, 2, and 5 hours after a 3-hour infusion. This was sufficient to obtain a Bayesian estimate of clearance a posteriori. Simulations showed the poor performance of a priori formula-based dose calculations with 90% of patients demonstrating a 69%-151% exposure interval around the target. This interval shrank to 85%-124% if TDM was carried out only at day 1 and to 90%-116% with TDM at days 1 and 3.
Conclusions: This comprehensive study reinforces the interest of TDM in managing interindividual variability in busulfan exposure. Therapeutic drug monitoring can reliably be implemented from 3 samples using the Bayesian approach, preferably over 2 days. If using the latter is not possible, the formulas developed herein could present an alternative in Thai patients.
期刊介绍:
Therapeutic Drug Monitoring is a peer-reviewed, multidisciplinary journal directed to an audience of pharmacologists, clinical chemists, laboratorians, pharmacists, drug researchers and toxicologists. It fosters the exchange of knowledge among the various disciplines–clinical pharmacology, pathology, toxicology, analytical chemistry–that share a common interest in Therapeutic Drug Monitoring. The journal presents studies detailing the various factors that affect the rate and extent drugs are absorbed, metabolized, and excreted. Regular features include review articles on specific classes of drugs, original articles, case reports, technical notes, and continuing education articles.