Pharmacogenetics of immunosuppressive drugs: prospect of individual therapy for transplant patients.
The immunosuppressive drugs used in solid-organ transplantation are potent and toxic agents with narrow therapeutic ranges. Underdosing is associated with immunological rejection of the transplanted organ, whereas overdosing results in infections, malignancy and direct toxicity to a number of organs. Pharmacokinetic heterogeneity makes initial dose determination difficult, as there is a poor correlation between dose and blood concentration. Therapeutic drug monitoring is available but the pharmacokinetic-pharmacodynamic association is imperfect and it does not help in achieving target blood concentrations during the critical early 2-3 days after transplantation. Genetic polymorphisms in drug targets, drug-metabolizing enzymes and drug efflux pumps have been identified as potential targets for developing a pharmacogenetic strategy to individualize initial drug choice and dose. To date, use of the CYP3A5 genotype to predict the appropriate initial dose of tacrolimus is the most promising option for individualization of drug therapy in organ transplantation.
Ekbal
Nasirul J
NJ
St George's, University of London, Cellular and Molecular Medicine: Renal Medicine, Cranmer Terrace, London SW170RE, UK.
Holt
David W
DW
Macphee
Iain Am
IA
D006084:Graft Rejection / Q000188:drug therapy* / Q000235:genetics* / Q000517:prevention & control; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D010597:Pharmacogenetics / Q000379:methods* / Q000639:trends; D011110:Polymorphism, Genetic / Q000187:drug effects / Q000235:genetics; D019737:Transplants / Q000639:trends
D007166:Immunosuppressive Agents