Cyclosporin binds to cyclophilin. The complex then inhibits calcineurin which is normally responsible for activating transcription of interleukin 2. Cyclosporin also inhibits lymphokine production and interleukin release. In ophthalmic applications, the precise mechanism of action is not known. Cyclosporin emulsion is thought to act as a partial immunomodulator in patients whose tear production is presumed to be suppressed due to ocular inflammation associated with keratoconjunctivitis sicca.
Used in immunosuppression for prophylactic treatment of organ transplants, cyclosporin exerts specific and reversible inhibition of immunocompetent lymphocytes in the G0-or G1-phase of the cell cycle. T-lymphocytes are preferentially inhibited. The T1-helper cell is the main target, although the T1-suppressor cell may also be suppressed. Sandimmune (cyclosporin) also inhibits lymphokine production and release including interleukin-2.
Hepatic, extensively metabolized.
The oral LD50 is 2329 mg/kg in mice, 1480 mg/kg in rats, and > 1000 mg/kg in rabbits. The I.V. LD50 is 148 mg/kg in mice, 104 mg/kg in rats, and 46 mg/kg in rabbits.
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