New immunosuppressive drugs: needs in and applications to pediatric transplantation.

The evolution of immunosuppressive therapy toward synergistic drug combinations seeks to minimize toxicity while potentiating efficacy. Median effect analysis discerns synergistic drug combinations that may be suitable for in vivo experiments in animals and for subsequent clinical trials. These studies suggest that two drugs rapamycin (RAPA) and brequinar (BQR) display synergistic effects in combination with cyclosporine. This combination must be evaluated for relative toxicity versus efficacy. Clinical trials to assess the individual toxicities of RAPA and BQR are presently underway in order to discern appropriate doses for randomized trials of clinical efficacy.