Preclinical evaluation of a new potent immunosuppressive agent, rapamycin.

Since individual immunosuppressive agents display pleiotropic arrays of nonimmunologic toxic complications when used at therapeutic concentrations, synergistic drug combinations proffer an attractive strategy. RAPA is a good candidate for this enterprise, because of its unique action to inhibit lymphokine signal transduction. Initial in vivo and in vitro studies using the rigorous pharmacologic tool, the median effect analysis, document a synergistic relation between RAPA and CsA in rodent and canine models. These preclinical findings compel careful Phase I trials, in order to assess the safety and synergistic efficacy of RAPA in combination drug regimens with other immunosuppressive agents.