Cyclosporine
Cyclosporine. Binds cyclophilin → inhibits calcineurin → blocks NFAT dephosphorylation → prevents T-cell IL-2 transcription. CYP3A4 + P-gp… Oral half-life 13 h.
Binds cyclophilin → inhibits calcineurin → blocks NFAT dephosphorylation → prevents T-cell IL-2 transcription. CYP3A4 + P-gp substrate — massive interaction list. Narrow therapeutic index; therapeutic drug monitoring mandatory.
PK: the worst-cited record in its batch — its source was a REVIEW that administered no route at all and whose abstract contains a single number, about a dosing threshold, with all six values hung on it. THE STORED 280 L IS ALSO A MATRIX ARTEFACT: it is 4.0 L/kg, the classic PLASMA figure, for a drug whose reference matrix is WHOLE BLOOD because it partitions into erythrocytes in a haematocrit-dependent way. Re-sourced to PMID:3058372, renal transplant recipients measured in whole blood by HPLC: "a volume of distribution of 2.88 +/- 1.1 L/kg" (202 L at 70 kg, intravenous-derived), "the bioavailability ranged from 0.11 to 0.47, with a mean value of 0.27", and "the elimination half-life was 12.8 +/- 3.8 hours". FORMULATION CAVEAT: no cited paper used NEORAL. Sandimmune absorption is saturable, its exposure rising "in a less than proportional manner with respect to dose", while the microemulsion is linear and delivers 174 to 239% of it — so one bioavailability cannot cover both products. A reference on this record contains no cyclosporine at all.
Pharmacokinetics
- Oral — t½ 12.8 h · F 27% · Vd 202 L
- IV — t½ 12.8 h · F 100% · Vd 202 L
Related compounds
- St. John's Wort — contraindicated
- Colchicine — contraindicated
- Berberine — major
- Rosuvastatin — major
- Atorvastatin — major
Sources: PMID:8513650, PMID:13129991, PMID:20190787, PMID:3203704, PMID:3058372, PMID:8165192