SDZ RAD, A NEW RAPAMYCIN DERIVATIVESynergism with Cyclosporine
作者:
Schuurman1,
Henk-Jan Cottens,
Sylvain Fuchs,
Serge Joergensen,
Joanne Meerloo,
Timo Sedrani,
Richard Tanner,
Madeleine Zenke,
Gerhard Schuler,
期刊:
Transplantation
(OVID Available online 1997)
卷期:
Volume 64,
issue 1
页码: 32-35
ISSN:0041-1337
年代: 1997
出版商: OVID
数据来源: OVID
摘要:
Background.SDZ RAD is a new rapamycin analog with potent immunosuppressive activity. Compounds of the rapamycin class differ in their mode of action from cyclosporine, thus providing a rationale for potential synergism of these two potent immunosuppressants.Methods.The two-way mouse mixed lymphocyte reaction (BALB/c-CBA strain combination) was applied. Orthotopic kidney and heterotopic heart allografting was performed in the stringent DA-to-Lewis rat strain combination, with administration of compounds orally as microemulsion preconcentrate (i.e., Neoral in the case of cyclosporine).Results.Isobologram analysis of checkerboard titrations of SDZ RAD and cyclosporine in two-way mouse mixed lymphocyte reactions indicates a synergistic interaction in vitro. In vivo, the minimal effective dose of microemulsion cyclosporine giving long-term graft survival was 5.0 mg/kg/day; for SDZ RAD, the minimal effective dose was 5.0 mg/kg/day in kidney transplantation and >5.0 mg/kg/day in heart transplantation. Long-term allograft survival was noted for combinations of microemulsion cyclosporine administered at 1.0 or 2.0 mg/kg/day and SDZ RAD given at between 0.5 and 2.0 mg/kg/day. The index of synergy in different combinations ranged between 0.3 and 0.7.Conclusions.SDZ RAD and cyclosporine show synergism in immunosuppression, both in vitro and in vitro. They form a promising synergistic drug combination in allotransplantation.
返 回