Lack of pharmacodynamic interaction between trimetazidine and cyclosporin A in human lymphoproliferative and mouse delayed hypersensitivity response models.
The hypothesis of an interaction between trimetazidine and the immunosuppressive effect of cyclosporin A was investigated in two models: a) ex vivo, the lymphoproliferative response of normal human lymphocytes to phytohemagglutinin and a murine monoclonal antibody against the CD3 T-lymphocyte membrane complex; b) in vivo, the delayed hypersensitivity response model in mouse. The uptake of methyl-3H-thymidine was measured in both models. For the lymphoproliferative response, statistical analysis showed that there was a significant inhibitory effect of cyclosporin A on cell proliferation (P < 0.001) and confidence intervals obtained by ANOVA showed the equivalence of the results when trimetazidine was combined with cyclosporin A (all CI95% < or = 10). In the delayed hypersensitivity model, cyclosporin A was also found to be very effective in inhibiting the immune response (P < 0.001), while trimetazidine did not interfere with cyclosporin A's effect. It was concluded that trimetazidine exerted neither an immunostimulatory nor an immunosuppressive effect in the two models, suggesting of the absence of interaction between trimetazidine and cyclosporin A's effectiveness when both drugs are given in combination.
Albengres
E
E
Service Hospitalo-Universitaire de Pharmacologie, Faculté de Médecine, Créteil, France.
Tillement
J P
JP
d'Athis
P
P
Salducci
D
D
Chauvet-Monges
A M
AM
Crevat
A
A
D000328:Adult; D000704:Analysis of Variance; D000818:Animals; D002478:Cells, Cultured / Q000187:drug effects; D016572:Cyclosporine / Q000493:pharmacokinetics / Q000494:pharmacology*; D004195:Disease Models, Animal; D004347:Drug Interactions; D005260:Female; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000139:chemically induced; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D066298:In Vitro Techniques; D008214:Lymphocytes / Q000187:drug effects; D008297:Male; D051379:Mice; D014292:Trimetazidine / Q000493:pharmacokinetics / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000493:pharmacokinetics / Q000494:pharmacology*
D007166:Immunosuppressive Agents; D014665:Vasodilator Agents; D016572:Cyclosporine; D014292:Trimetazidine