THE USE OF THERAPEUTIC DRUG-MONITORING TO OPTIMIZE IMMUNOSUPPRESSIVE THERAPY

Most experience of the therapeutic drug monitoring of immunosuppressiv e agents has been acquired in the field of solid organ transplantation ; however, agents such as cyclosporin (cyclosporin A) are being increa singly utilised for the management of autoimmune diseases. Cyclosporin is the most widely studied immunosuppressant, but in spite of this ma ny controversies still exist as to the optimum strategy for monitoring this drug. Owing to its widely variable pharmacokinetics and metaboli sm, and the absence of a simple method to measure therapeutic effectiv eness, many factors should be considered. In most circumstances, measu ring whole blood trough concentrations of cyclosporin with a specific assay methodology is warranted. In addition, knowledge of other factor s that may alter the pharmacokinetics (such as liver function, concomi tant food or medications, gastrointestinal status, and time since tran splantation) should be taken into account so that therapy can be appro priately adjusted. Other methods of monitoring have been investigated, such as AUC (area under the concentration-time curve) monitoring and immunological monitoring. However, further refinement of these techniq ues and greater experience with their efficacy must be accumulated bef ore their role in the monitoring of cyclosporin can be defined. Tacrol imus, like cyclosporin, shares many of the difficulties in monitoring for efficacy and toxicity due largely to the variable pharmacokinetics ; similarly to cyclosporin, whole blood trough concentration monitorin g should be utilised in combination with knowledge of the factors that may affect the pharmacokinetics. Muromonab CD3 (OKT3) is a monoclonal antibody used for the treatment and prophylaxis of acute allograft re jection. Several immunological monitoring techniques have been investi gated for this agent. Monitoring CD3+ levels can assist clinicians in determining therapeutic efficacy, while measuring anti-muromonab CD3 a ntibody titres can help determine if xenosensitisation has occurred, c ausing therapeutic ineffectiveness. The clinical monitoring of azathio prine, one of the first immunosuppressive agents used in transplantati on, has historically been limited to monitoring complete blood counts for bone marrow suppression. However, newer techniques measuring intra cellular DNA nucleotides appear to be promising. The new immunosuppres sants on the horizon include mycophenolate mofetil and rapamycin. The clinical experience with therapeutic drug monitoring of these 2 compou nds is scant in the literature; however, both agents have demonstrated efficacy in preventing or treating allograft rejection while maintain ing a relatively well tolerated toxicity profile in recent clinical tr ials. Routine monitoring does not appear to be warranted for immunosup pressive therapy in autoimmune diseases.