Prospects for synergistic immunosuppressive drug therapy in the coming decade.
The major clinical strategy during the past three decades has been to discover a single drug that achieves immunosuppression with minimal toxic side effects. Regimens to optimize CyA immunosuppressive therapy have been limited by marked interindividual variations in drug pharmacokinetics and pharmacodynamics that cause simple drug administration routines to produce variable clinical outcomes. The approach presented herein seeks to employ multiple immunosuppressive agents that act synergistically to inhibit alloactivation. Using the rigorous median effect analysis, synergistic interactions have been discerned both using in vitro systems, as well as in vivo transplant situations. CyA has a profoundly synergistic interaction with RAPA, and a moderately synergistic effect with QCA. The next decade presents important opportunities to determine whether these immunologic effects are beclouded by synergistic drug toxicities. Studies of this type may allow us to achieve a uniformly effective, yet well-tolerated, immunosuppressive regimens in the future.
Kahan
B D
BD
Department of Surgery, University of Texas Medical School, Houston 77030.
Gibbons-Stubber
S
S
Tejpal
N
N
Chou
T C
TC
D016572:Cyclosporine / Q000008:administration & dosage*; D004347:Drug Interactions; D004357:Drug Synergism; D007165:Immunosuppression Therapy / Q000379:methods*; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D008213:Lymphocyte Activation / Q000187:drug effects; D008222:Lymphokines / Q000502:physiology; D009696:Nucleic Acids / Q000096:biosynthesis; D015398:Signal Transduction
D007166:Immunosuppressive Agents; D008222:Lymphokines; D009696:Nucleic Acids; D016572:Cyclosporine