[Neoral (Cyclosporin microemulsion preconcentrate): pharmacokinetics, pharmacodynamics and its improved clinical outcome].
Sandimmun displays considerable inter- and intra-patient variability because its absorption is bile-dependent and affected by concomitant intake of food. Neoral is a microemulsion preconcentrate; a microemulsion is a mixture of the lipophilic active substance with accurately balanced amounts of lipophilic solvent, hydrophilic solvent and surfactant. As the result of advanced microemulsion technique, Neoral has more consistent and improved absorption characteristics. Cyclosporin (cyclosporin A) has been used as an immunosuppressive agent. The major pharmacodynamic action of cyclosporin within T cells is calcineurin inhibition. The complex cyclophilin-cyclosporin competitively binds to the Ca(2+)- and calmodulin-dependent phosphatase calcineurin which then inhibits downstream dephosphorylation and activation of NFAT(transcription factor). The greatest calcineurin inhibition is seen 1-2 h after administration of Neoral in parallel to the highest blood concentration. Variability in cyclosporin exposure was also identified as a risk factor for acute rejection in organ transplant recipients. "Absorption profiling" provides a more accurate prediction of drug exposure and leads to less acute rejection and toxicity. The evolution of Neoral monitoring strategies from trough level to absorption profile will raise the standard of performance of Neoral, resulting in clinical benefits for transplant patients.
Nishi
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Y
Novartis Pharma K.K., 4-17-30 Nishiazabu, Minatoku, Tokyo 106-8618, Japan. yoko.nishi@pharma.novartis.com
D000818:Animals; D065095:Calcineurin Inhibitors; D002986:Clinical Trials as Topic; D016572:Cyclosporine / Q000493:pharmacokinetics* / Q000494:pharmacology* / Q000627:therapeutic use; D016903:Drug Monitoring; D004655:Emulsions; D006084:Graft Rejection / Q000517:prevention & control; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics* / Q000494:pharmacology* / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000276:immunology
D065095:Calcineurin Inhibitors; D004655:Emulsions; D007166:Immunosuppressive Agents; D016572:Cyclosporine