title: Pharmacogenetics and immunosuppressive drugs in solid organ transplantation.
abstract: 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.
authors.affiliation: Department of Hospital Pharmacy, Erasmus MC, University Medical Center Rotterdam, P.O. Box 2040, 3000 CA Rotterdam, Netherlands.
authors.forename: Teun
authors.initials: T
authors.lastname: van Gelder
authors.affiliation: Department of Clinical Chemistry, Erasmus MC, University Medical Center Rotterdam, P.O. Box 2040, 3000 CA Rotterdam, Netherlands.
authors.forename: Ron H
authors.initials: RH
authors.lastname: van Schaik
authors.affiliation: Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, P.O. Box 2040, 3000 CA Rotterdam, Netherlands.
authors.forename: Dennis A
authors.initials: DA
authors.lastname: Hesselink
mesh_terms: D001379:Azathioprine / Q000493:pharmacokinetics / Q000627:therapeutic use; D016572:Cyclosporine / Q000493:pharmacokinetics / Q000627:therapeutic use; D016903:Drug Monitoring; D000068338:Everolimus; D019317:Evidence-Based Medicine; D005260:Female; D006084:Graft Rejection / Q000235:genetics* / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects / Q000235:genetics; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000009:adverse effects / Q000379:methods; D008297:Male; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000627:therapeutic use; D016377:Organ Transplantation / Q000009:adverse effects* / Q000379:methods; D010597:Pharmacogenetics / Q000379:methods*; D011110:Polymorphism, Genetic; D011237:Predictive Value of Tests; D020123:Sirolimus / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000627:therapeutic use; D016559:Tacrolimus / Q000493:pharmacokinetics / Q000627:therapeutic use; D014181:Transplantation Immunology / Q000187:drug effects* / Q000235:genetics
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine; D000068338:Everolimus; D009173:Mycophenolic Acid; D001379:Azathioprine; D020123:Sirolimus; D016559:Tacrolimus