Cyclosporine: a review of drug monitoring problems and presentation of a simple, accurate liquid chromatographic procedure that solves these problems.

Many studies involving large numbers of patients prove the efficacy of cyclosporine to accomplish immunosuppression following hetertopic organ transplant. In long-term follow-up, cyclosporine produces a higher level of nephropathy than does conventional immunosuppression consisting of azathioprine and prednisone. The degree of nephropathy appears to be related to blood concentration and the effect can be minimized by maintaining therapeutic trough blood concentrations. Other significant side effects (central nervous system toxicity and hirsutism) can also be minimized by low blood concentrations. Development of lymphoma secondary to Epstein-Barr virus exposure is unrelated to blood concentration. Two methods are available for therapeutic drug monitoring: radioimmunoassay (RIA) and high pressure liquid chromatography (HPLC). RIA on plasma is a standard, rapid means of obtaining a result, but that result is inaccurate due to metabolite cross-reactivity. The concentration of cyclosporine in plasma is widely variable and unrepresentative of the whole blood concentration. Plasma concentration is dependent upon the temperature of plasma separation. Whole blood analysis avoids this problem. HPLC procedures allow for whole blood analysis but are tedious and time-consuming. We present here a simple, accurate HPLC procedure that is reproducible (CV = 4.9%), sensitive (to 50 ng/mL), and fast (preparation time - 5.7 minutes, chromatography time - 20 minutes). This procedure correlates (r = 0.98) with a reference HPLC procedure and has been used in our clinical laboratory for analysis of more than 4000 specimens without apparent problem. No interferences have been identified.