BACKGROUND: The immunosuppressive drugs used worldwide have a narrow therapeutic index, which results in a need to individualize the dose regimen for different recipients. The oxidative enzymes cytochrome P450 (CYP)3A...BACKGROUND: The immunosuppressive drugs used worldwide have a narrow therapeutic index, which results in a need to individualize the dose regimen for different recipients. The oxidative enzymes cytochrome P450 (CYP)3A and the drug efflux pump P-glycoprotein (P-gp) are two potential factors in the processes of metabolism. Pharmacogenetic study of immunosuppressive drugs has focused on these two enzymes. This review was undertaken to assess the role of single nuclear polymorphisms (SNPs) of these two enzymes in the individual administration of immunosuppressive drugs. DATA SOURCES: An English-language literature search was made using MEDLINE for articles on CYP3A and P-gp in organ transplantation. RESULTS: The SNPs of CYP3A and P-gp are closely correlated to the large variations of cyclosporine and tacrolimus dosage between different patients, although conflicting results were obtained by some authors. CONCLUSIONS: More studies should be conducted to elucidate further the pharmacogenetics of immunosuppressive drugs in organ transplantation, a deep understanding of which would provide an important step toward drug regimen individualization in the posttransplant therapy.展开更多
目的对群体药动学的方法在优化万古霉素个体化给药方案中的应用进行分析。方法收集2020年9月-2022年10月入住上海市嘉定区中心医院并接受万古霉素治疗的患者40例,根据万古霉素群体药动学(PPK)研究模型,采用群体药动学软件Java PK for de...目的对群体药动学的方法在优化万古霉素个体化给药方案中的应用进行分析。方法收集2020年9月-2022年10月入住上海市嘉定区中心医院并接受万古霉素治疗的患者40例,根据万古霉素群体药动学(PPK)研究模型,采用群体药动学软件Java PK for desktop(JPKD),输入患者个体情况(体重、年龄、肌酐)、万古霉素初始方案和第1次万古霉素稳态血药谷浓度(Css,min)。利用贝叶斯反馈法方法估算药动学参数,根据给出的方案调整患者用药,计算调整方案的(Css,min)预测值,达稳态后测得调整方案的(Css,min)实测值,考察(Css,min)预测值与(Css,min)实测值的相关性。结果纳入40例患者,(Css,min)初始值为(6.37±1.43)μg/ml,调整后(Css,min)实测值为(13.65±2.58)μg/ml,(Css,min)预测值为(13.11±1.16)μg/ml。调整后(Css,min)实测值与(Css,min)预测值比较,差异无统计学意义(P>0.05)。调整后(Css,min)实测值与(Css,min)预测值有显著相关性(r=0.531,P<0.05)。结论群体药动学软件可以根据患者的个体情况调整万古霉素的给药方案,具有良好的血药浓度预测性。展开更多
基金This study was supported by a grant from the 973 National Basic Research Program of China (2003CB515501)
文摘BACKGROUND: The immunosuppressive drugs used worldwide have a narrow therapeutic index, which results in a need to individualize the dose regimen for different recipients. The oxidative enzymes cytochrome P450 (CYP)3A and the drug efflux pump P-glycoprotein (P-gp) are two potential factors in the processes of metabolism. Pharmacogenetic study of immunosuppressive drugs has focused on these two enzymes. This review was undertaken to assess the role of single nuclear polymorphisms (SNPs) of these two enzymes in the individual administration of immunosuppressive drugs. DATA SOURCES: An English-language literature search was made using MEDLINE for articles on CYP3A and P-gp in organ transplantation. RESULTS: The SNPs of CYP3A and P-gp are closely correlated to the large variations of cyclosporine and tacrolimus dosage between different patients, although conflicting results were obtained by some authors. CONCLUSIONS: More studies should be conducted to elucidate further the pharmacogenetics of immunosuppressive drugs in organ transplantation, a deep understanding of which would provide an important step toward drug regimen individualization in the posttransplant therapy.
文摘目的对群体药动学的方法在优化万古霉素个体化给药方案中的应用进行分析。方法收集2020年9月-2022年10月入住上海市嘉定区中心医院并接受万古霉素治疗的患者40例,根据万古霉素群体药动学(PPK)研究模型,采用群体药动学软件Java PK for desktop(JPKD),输入患者个体情况(体重、年龄、肌酐)、万古霉素初始方案和第1次万古霉素稳态血药谷浓度(Css,min)。利用贝叶斯反馈法方法估算药动学参数,根据给出的方案调整患者用药,计算调整方案的(Css,min)预测值,达稳态后测得调整方案的(Css,min)实测值,考察(Css,min)预测值与(Css,min)实测值的相关性。结果纳入40例患者,(Css,min)初始值为(6.37±1.43)μg/ml,调整后(Css,min)实测值为(13.65±2.58)μg/ml,(Css,min)预测值为(13.11±1.16)μg/ml。调整后(Css,min)实测值与(Css,min)预测值比较,差异无统计学意义(P>0.05)。调整后(Css,min)实测值与(Css,min)预测值有显著相关性(r=0.531,P<0.05)。结论群体药动学软件可以根据患者的个体情况调整万古霉素的给药方案,具有良好的血药浓度预测性。
