Pharmacogenetics and immunosuppressive drugs in solid organ transplantation

被引:76
|
作者
van Gelder, Teun [1 ]
van Schaik, Ron H. [2 ]
Hesselink, Dennis A. [3 ]
机构
[1] Univ Med Ctr Rotterdam, Erasmus MC, Dept Hosp Pharm, NL-3000 CA Rotterdam, Netherlands
[2] Univ Med Ctr Rotterdam, Erasmus MC, Dept Clin Chem, NL-3000 CA Rotterdam, Netherlands
[3] Univ Med Ctr Rotterdam, Erasmus MC, Dept Internal Med, NL-3000 CA Rotterdam, Netherlands
关键词
MONOPHOSPHATE DEHYDROGENASE-ACTIVITY; SINGLE-NUCLEOTIDE POLYMORPHISMS; THIOPURINE S-METHYLTRANSFERASE; IMPLEMENTATION CONSORTIUM GUIDELINES; INHIBITOR-RELATED NEPHROTOXICITY; ELECTRONIC MEDICAL-RECORDS; RENAL-ALLOGRAFT RECIPIENTS; CLINICAL DECISION-SUPPORT; TROUGH BLOOD-LEVELS; MYCOPHENOLIC-ACID;
D O I
10.1038/nrneph.2014.172
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
The transplantation literature includes numerous papers that report associations between polymorphisms in genes encoding metabolizing enzymes and drug transporters, and pharmacokinetic data on immunosuppressive drugs. Most of these studies are retrospective in design, and although a substantial number report significant associations, pharmacogenetic tests are hardly used in clinical practice. One of the reasons for this poor implementation is the current lack of evidence of improved clinical outcome with pharmacogenetic testing. Furthermore, with efficient therapeutic drug monitoring it is possible to rapidly correct for the effect of genotypic deviations on pharmacokinetics, thereby decreasing the utility of genotype-based dosing. The future of pharmacogenetics will be in treatment models in which patient characteristics are combined with data on polymorphisms in multiple genes. These models should focus on pharmacodynamic parameters, variations in the expression of drug transporter proteins, and predictors of toxicity. Such models will provide more information than the relatively small candidate gene studies performed so far. For implementation of these models into clinical practice, linkage of genotype data to medication prescription systems within electronic health records will be crucial.
引用
收藏
页码:725 / 731
页数:7
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