Therapeutic drug monitoring of immunosuppressive drugs in kidney transplantation.
OBJECTIVE
Drug monitoring has become an accepted adjunct to optimizing therapy with immunosuppressive drugs. This review assesses publications that relate to the analytical techniques used to measure cyclosporin, tacrolimus, mycophenolic acid, sirolimus and everolimus, as well as the clinical data obtained for these drugs. For all of these drugs there has been a substantial and continuing investment in assessing the clinical value of drug monitoring.


RESULTS
Fundamental controversies still persist regarding which time point to use for monitoring. The most significant single development has been the move towards using a timed blood sample 2 h after drug administration (C2) to monitor cyclosporin therapy with the Neoral formulation. The favourable clinical results obtained with this approach have had an impact on reevaluating monitoring data for some of the other drugs. The newest drugs to reach clinical evaluation, sirolimus and everolimus, have been studied in the context of concentration-controlled dosing and there is a good rationale for their measurement. There have also been developments in the analytical techniques used, mostly to improve the selectivity of the assays or to adapt them to new monitoring strategies.


CONCLUSIONS
Interpretation of drug concentration data is becoming ever more complex in this field as the number of potential drug combinations expands. The relatively narrow therapeutic index of these agents and the ever-present risk of clinically significant pharmacokinetic drug interactions makes drug monitoring an important aspect of their prescription.
Holt
David W
DW
Analytical Unit, St George's Hospital Medical School, London, UK. d.holt@sghms.ac.uk
D000818:Animals; D016572:Cyclosporine / Q000097:blood / Q000493:pharmacokinetics; D016903:Drug Monitoring; D000068338:Everolimus; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood* / Q000493:pharmacokinetics; D016030:Kidney Transplantation / Q000276:immunology*; D009173:Mycophenolic Acid / Q000097:blood / Q000493:pharmacokinetics; D020123:Sirolimus / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics; D016559:Tacrolimus / Q000097:blood / Q000493:pharmacokinetics
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D000068338:Everolimus; D009173:Mycophenolic Acid; D020123:Sirolimus; D016559:Tacrolimus