The interaction between FK778 and tacrolimus in the prevention of rat cardiac allograft rejection is dose dependent
Standard
The interaction between FK778 and tacrolimus in the prevention of rat cardiac allograft rejection is dose dependent. / Deuse, Tobias; Schrepfer, Sonja; Reichenspurner, Hermann.
in: TRANSPLANTATION, Jahrgang 77, Nr. 4, 27.02.2004, S. 509-513.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - The interaction between FK778 and tacrolimus in the prevention of rat cardiac allograft rejection is dose dependent
AU - Deuse, Tobias
AU - Schrepfer, Sonja
AU - Reichenspurner, Hermann
PY - 2004/2/27
Y1 - 2004/2/27
N2 - OBJECTIVE: The synthetic malononitrilamide FK778 inhibits T- and B-cell responsiveness, phagocyte effector function, exerts inhibitory activity against cytomegalovirus, and is thus one of the most promising new immunosuppressive drugs. The aim of this study was to evaluate the combination of FK778 and tacrolimus in a high-responder rat cardiac transplantation model.METHODS: The Brown Norway-Lewis rat strain combination was used to investigate graft survival after 10 days of posttransplant oral therapy with FK778 (5 or 20 mg/kg), tacrolimus (2 or 8 mg/kg), or combination regimens at varying doses (5+2 mg/kg, 10+1 mg/kg, or 20+8 mg/kg). Grafts were harvested after cessation of cardiac contractions. Combination indices (CI) were calculated for drug combinations.RESULTS: In untreated recipients, allograft survival was 6.2+/-0.4 days. FK778 at 20 mg/kg and tacrolimus at 2 or 8 mg/kg significantly prolonged graft survival to a mean survival time (MST) of 17.0+/-2.8, 18.5+/-2.7, and 25.0+/-2.5 days, respectively. The two low-dose drug combinations achieved a graft survival of 23.2+/-2.9 and 25.2+/-3.1 days, which was significantly longer compared with FK778 at 5 mg/kg, FK778 at 20 mg/kg, and tacrolimus at 2 mg/kg (P CONCLUSIONS: This study provides evidence that FK778 and tacrolimus show supportive interaction in their immunosuppressive potency that is synergistic in low-dose combinations and additive in higher doses.
AB - OBJECTIVE: The synthetic malononitrilamide FK778 inhibits T- and B-cell responsiveness, phagocyte effector function, exerts inhibitory activity against cytomegalovirus, and is thus one of the most promising new immunosuppressive drugs. The aim of this study was to evaluate the combination of FK778 and tacrolimus in a high-responder rat cardiac transplantation model.METHODS: The Brown Norway-Lewis rat strain combination was used to investigate graft survival after 10 days of posttransplant oral therapy with FK778 (5 or 20 mg/kg), tacrolimus (2 or 8 mg/kg), or combination regimens at varying doses (5+2 mg/kg, 10+1 mg/kg, or 20+8 mg/kg). Grafts were harvested after cessation of cardiac contractions. Combination indices (CI) were calculated for drug combinations.RESULTS: In untreated recipients, allograft survival was 6.2+/-0.4 days. FK778 at 20 mg/kg and tacrolimus at 2 or 8 mg/kg significantly prolonged graft survival to a mean survival time (MST) of 17.0+/-2.8, 18.5+/-2.7, and 25.0+/-2.5 days, respectively. The two low-dose drug combinations achieved a graft survival of 23.2+/-2.9 and 25.2+/-3.1 days, which was significantly longer compared with FK778 at 5 mg/kg, FK778 at 20 mg/kg, and tacrolimus at 2 mg/kg (P CONCLUSIONS: This study provides evidence that FK778 and tacrolimus show supportive interaction in their immunosuppressive potency that is synergistic in low-dose combinations and additive in higher doses.
KW - Alkynes
KW - Animals
KW - Dose-Response Relationship, Drug
KW - Drug Synergism
KW - Graft Rejection/prevention & control
KW - Graft Survival
KW - Heart Transplantation
KW - Immunosuppressive Agents/administration & dosage
KW - Isoxazoles/administration & dosage
KW - Male
KW - Nitriles
KW - Rats
KW - Rats, Inbred BN
KW - Tacrolimus/administration & dosage
U2 - 10.1097/01.tp.0000113443.70993.8c
DO - 10.1097/01.tp.0000113443.70993.8c
M3 - SCORING: Journal article
C2 - 15084926
VL - 77
SP - 509
EP - 513
JO - TRANSPLANTATION
JF - TRANSPLANTATION
SN - 0041-1337
IS - 4
ER -