Does pharmacogenetics have the potential to allow the individualisation of immunosuppressive drug dosing in organ transplantation?
The immunosuppressive drugs used in organ transplantation have a narrow therapeutic index, with rejection occurring as a consequence of underdosing and infection, malignancy and a number of drug-specific side effects with excessive dosing. Significant heterogeneity in the dose of drug required to achieve therapeutic blood concentrations adds to the complexity of the problem, which has been partly resolved by therapeutic drug monitoring. Single nucleotide polymorphisms have been identified in genes encoding metabolic enzymes, drug efflux pumps and drug targets for most of the drugs in widespread use. A pharmacogenetic approach to immunosuppressive drug prescribing remains to be tested. Based on current evidence, the most promising strategy would be use of the cytochrome P450 3A5 expressor genotype to guide initial dosing with tacrolimus.
MacPhee
Iain A M
IA
Cellular and Molecular Medicine, Renal Medicine, St. George's Hospital, University of London, Cranmer Terrace, London, SW17 0RE, UK. imacphee@sgul.ac.uk
Fredericks
Salim
S
Holt
David W
DW
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D016377:Organ Transplantation / Q000379:methods / Q000639:trends*; D010597:Pharmacogenetics / Q000379:methods / Q000639:trends*
D007166:Immunosuppressive Agents