Optimizing cyclosporine therapy: dose, levels, and monitoring

The use of CsA has evolved considerably in concept and practice since the First International Congress on this drug in 1983. CsA is now increasingly used as a component of a multiagent protocol, rather than as a single, potent agent, with adjunctive therapy selected to optimize induction or maintenance immunosuppression. Novel clinical developments include the prophylactic use of the MoAb OKT3 as an alternative to polyclonal ALG, and the coadministration of bromocriptine to inhibit prolactin-dependent immune augmentation. Other combinations with site-selective pharmacologic agents are now under investigation in vitro or in vivo to improve both the selectivity and potency of immunosuppression while reducing further the toxicity and cost of CsA. With the introduction of MoAb to CsA, rapid and specific measurement of the parent molecule will now become widely possible. Because of its simplicity and rapidity, this technique may well replace HPLC for routine monitoring, although the latter will remain indispensable in a research setting for measurement of individual metabolites. Specific measurement of the parent molecule is clearly important in heart or liver transplantation when hepatic metabolism is frequently grossly disturbed. There is less evidence that this will prove of value in renal transplantation, however, and it remains possible that by virtue of the biologic effect of certain metabolites, a more broadly crossreactive polyclonal assay is equal or superior in this setting. In this regard, the fluorescence polarization immunoassay is particularly attractive as a clinical monitoring system. It is simple, accurate, and cost-effective, and by virtue of its automation and speed, particularly adapted to outpatient monitoring. The planned introduction of new kits allowing measurement by monoclonal or polyclonal antibody in either serum or whole blood will make this a versatile system for the measurement of CsA.