Use of pharmacogenetics to optimize immunosuppressive therapy.
Pharmacogenetic strategies offer promise as an adjunct to therapeutic drug monitoring in achieving target blood concentrations of the immunosuppressive drugs as early as possible after transplantation. To date, the only strategy to have been tested in a clinical trial is the use of the cytochrome P450 3A5 (CYP3A5) genotype to predict tacrolimus dose. Other potential candidates are CYP3A5 and sirolimus and UGT1A9 for mycophenolate. There are also genetic predictors of pharmacodynamics, including IMPDH1 for mycophenolate and ABCB1 for cyclosporine that may identify individuals at particular risk of efficacy failure or toxicity with a given drug. As pharmacogenetic testing moves into routine clinical practice, standards for service delivery and reporting of results need to be established.
Macphee
Iain A M
IA
St. George's, University of London, London, UK. imacphee@sgul.ac.uk
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000097:blood / Q000235:genetics; D016572:Cyclosporine / Q000097:blood; D051544:Cytochrome P-450 CYP3A / Q000097:blood* / Q000235:genetics; D005838:Genotype; D006801:Humans; D007168:IMP Dehydrogenase / Q000097:blood / Q000235:genetics; D007165:Immunosuppression Therapy / Q000379:methods; D007166:Immunosuppressive Agents / Q000097:blood* / Q000493:pharmacokinetics; D016030:Kidney Transplantation / Q000276:immunology; D010597:Pharmacogenetics / Q000379:methods*; D011110:Polymorphism, Genetic / Q000276:immunology; D020123:Sirolimus / Q000097:blood; D016559:Tacrolimus / Q000097:blood*
C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D007168:IMP Dehydrogenase; C488211:IMPDH1 protein, human; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A; D020123:Sirolimus; D016559:Tacrolimus