SDZ RAD, a new rapamycin derivative: synergism with cyclosporine.
Transplantation
; 64(1): 32-5, 1997 Jul 15.
Article
em En
| MEDLINE
| ID: mdl-9233697
ABSTRACT
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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Polienos
/
Imunossupressores
Limite:
Animals
Idioma:
En
Revista:
Transplantation
Ano de publicação:
1997
Tipo de documento:
Article
País de afiliação:
Suíça