Pharmacokinetic and pharmacodynamic monitoring of immunosuppressive drugs in solid organ transplant recipients

Abstract

Current clinical immunosuppressive regimens consist of combinations of drugs, in order to allow a reduction in the individual drug doses as a means to widen the therapeutic interval and to reduce the likelihood of individual drug toxicity. Combining drugs with different mechanisms of action may result in additive or even synergistic effects, potentially allowing dose reduction of individual drugs. Within the field of solid organ transplantation there is an unprecedented interest in therapeutic drug monitoring of immunosuppressive drugs, not only for recently introduced drugs, but also for established agents such as azathioprine and cyclosporine. Pharmacokinetic monitoring usually focuses on reaching certain target drug concentrations. Such ranges have been developed by retrospective review of drug concentration data and their correlation with clinical outcome. Multicenter concentration-controlled clinical trials can provide a basis for designing future prospective TDM investigations. Ideally, added to these trials should be also one or more pharmacodynamic tests, to quantify the biological effect of the drugs applied. Although on theoretical grounds monitoring the pharmacodynamic effect makes more sense than monitoring drug concentrations, in daily practice pharmacodynamic monitoring is not performed. Defining optimal ranges for pharmacokientic and pharmacodynamic drug monitoring of immunosuppressive drugs may lead to further improvement of the safety and efficacy of our immunosuppressive regimens.