{"title":"用有限采样模型估算造血干细胞移植受者体内霉酚酸的曲线下面积。","authors":"Liangmo Lin, Mianhui Hong, Xiangjun Fu","doi":"10.1002/bdd.2399","DOIUrl":null,"url":null,"abstract":"<p><p>Relationship between the areas under the curve (AUC) of mycophenolic acid (MPA) and the likelihood of rejection is well-established in solid organ transplantation recipients. In hematopoietic stem cell transplantation (HSCT), MPA AUC is also linked to graft versus host disease. This study aimed to develop a simplified method to estimate MPA AUC<sub>0-12</sub> in Chinese patients undergoing allogeneic HSCT (allo-HSCT). Intensive sampling was conducted in 22 patients who were orally administered mycophenolate mofetil. Plasma concentrations of total MPA were measured, and a model predicting AUC<sub>0-12</sub> using data from these 22 patients was constructed through regression analysis. The accuracy of the most suitable model was assessed in an additional 20 patients. None of the individual MPA concentrations showed a strong correlation with AUC<sub>0-12</sub> (r<sup>2</sup> < 0.7). Models utilizing 4 or more concentrations were found to effectively estimate MPA AUC<sub>0-12</sub> (r<sup>2</sup> > 0.87). The most operationally feasible model demonstrated good predictive performance with a mean absolute percentage error (APE%) < 20%. Single MPA concentrations showed poor correlation with MPA AUC<sub>0-12</sub>. A model utilizing 4 oral concentrations (0, 0.5, 1, and 4 h postdose) over a 12-h period could effectively estimate MPA AUC<sub>0-12</sub> with precise results and minimal bias.</p>","PeriodicalId":8865,"journal":{"name":"Biopharmaceutics & Drug Disposition","volume":null,"pages":null},"PeriodicalIF":1.7000,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"A limited sampling model to estimate the area under the curve of mycophenolic acid in hematopoietic stem cell transplantation recipients.\",\"authors\":\"Liangmo Lin, Mianhui Hong, Xiangjun Fu\",\"doi\":\"10.1002/bdd.2399\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Relationship between the areas under the curve (AUC) of mycophenolic acid (MPA) and the likelihood of rejection is well-established in solid organ transplantation recipients. In hematopoietic stem cell transplantation (HSCT), MPA AUC is also linked to graft versus host disease. This study aimed to develop a simplified method to estimate MPA AUC<sub>0-12</sub> in Chinese patients undergoing allogeneic HSCT (allo-HSCT). Intensive sampling was conducted in 22 patients who were orally administered mycophenolate mofetil. Plasma concentrations of total MPA were measured, and a model predicting AUC<sub>0-12</sub> using data from these 22 patients was constructed through regression analysis. The accuracy of the most suitable model was assessed in an additional 20 patients. None of the individual MPA concentrations showed a strong correlation with AUC<sub>0-12</sub> (r<sup>2</sup> < 0.7). Models utilizing 4 or more concentrations were found to effectively estimate MPA AUC<sub>0-12</sub> (r<sup>2</sup> > 0.87). The most operationally feasible model demonstrated good predictive performance with a mean absolute percentage error (APE%) < 20%. Single MPA concentrations showed poor correlation with MPA AUC<sub>0-12</sub>. A model utilizing 4 oral concentrations (0, 0.5, 1, and 4 h postdose) over a 12-h period could effectively estimate MPA AUC<sub>0-12</sub> with precise results and minimal bias.</p>\",\"PeriodicalId\":8865,\"journal\":{\"name\":\"Biopharmaceutics & Drug Disposition\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":1.7000,\"publicationDate\":\"2024-09-26\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Biopharmaceutics & Drug Disposition\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1002/bdd.2399\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biopharmaceutics & Drug Disposition","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1002/bdd.2399","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
A limited sampling model to estimate the area under the curve of mycophenolic acid in hematopoietic stem cell transplantation recipients.
Relationship between the areas under the curve (AUC) of mycophenolic acid (MPA) and the likelihood of rejection is well-established in solid organ transplantation recipients. In hematopoietic stem cell transplantation (HSCT), MPA AUC is also linked to graft versus host disease. This study aimed to develop a simplified method to estimate MPA AUC0-12 in Chinese patients undergoing allogeneic HSCT (allo-HSCT). Intensive sampling was conducted in 22 patients who were orally administered mycophenolate mofetil. Plasma concentrations of total MPA were measured, and a model predicting AUC0-12 using data from these 22 patients was constructed through regression analysis. The accuracy of the most suitable model was assessed in an additional 20 patients. None of the individual MPA concentrations showed a strong correlation with AUC0-12 (r2 < 0.7). Models utilizing 4 or more concentrations were found to effectively estimate MPA AUC0-12 (r2 > 0.87). The most operationally feasible model demonstrated good predictive performance with a mean absolute percentage error (APE%) < 20%. Single MPA concentrations showed poor correlation with MPA AUC0-12. A model utilizing 4 oral concentrations (0, 0.5, 1, and 4 h postdose) over a 12-h period could effectively estimate MPA AUC0-12 with precise results and minimal bias.
期刊介绍:
Biopharmaceutics & Drug Dispositionpublishes original review articles, short communications, and reports in biopharmaceutics, drug disposition, pharmacokinetics and pharmacodynamics, especially those that have a direct relation to the drug discovery/development and the therapeutic use of drugs. These includes:
- animal and human pharmacological studies that focus on therapeutic response. pharmacodynamics, and toxicity related to plasma and tissue concentrations of drugs and their metabolites,
- in vitro and in vivo drug absorption, distribution, metabolism, transport, and excretion studies that facilitate investigations related to the use of drugs in man
- studies on membrane transport and enzymes, including their regulation and the impact of pharmacogenomics on drug absorption and disposition,
- simulation and modeling in drug discovery and development
- theoretical treatises
- includes themed issues and reviews
and exclude manuscripts on
- bioavailability studies reporting only on simple PK parameters such as Cmax, tmax and t1/2 without mechanistic interpretation
- analytical methods