I am testing a compound that might be immunosuppressive and I am using cyclosporine as a positive control. Based on the literature, I am planning on injecting mice i.p with 30 mg/kg/day of cyclosporine for 10 days. Does this sound reasonable? Has anyone else done this?
Hi Luisa, one rational approach to select an optimal cyclosporine dosage regimen involves consideration of the blood/action site concentrations achieved in the mice following i.p. dosing of your regimen, in relation to an estimate of its EC50 (conc. producing 50% maximal effect) observed in an immunosuppression-based assay. Ideally, your dosing design should yield an exposure that is above or equal to the EC50 to observe a robust immunosuppressive response.
Attached are two articles that may provide relevant information on the pharmacokinetics of CsA as well as info on the IC50 of CsA in a lymphocyte suppression assay. Good luck!
Induction of Immunosuppression
Cyclosporine: 3 to 6 mg / kg body weight 2 times / day, orally. The oral dose should be controlled weekly in the first 3 months, either by time zero (C0) or trough level (result obtained in blood collected fasting 12 hours after the last administration and should range from 200 to 300 ng / mL) or by C2 or peak (result obtained in blood collected 2 hours after the morning and should be between 800 and 1200 ng / mL). after the first year of transplantation, the recommended serum level is lower and should range from 500 and 800 ng / mL.
The results depend on the weight, the dose administered and the immunosuppression desired for (transplants, autoimmune diseases).
I suggest you read: Transplantation. 1990 Jan;49(1):30-4.The impact of steady-state cyclosporine concentrations on renal allograft outcome.
Dunn J1, Grevel J, Napoli K, Lewis RM, Van Buren CT, Kahan BD.
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