Advances in Cyclosporine Pharmacology, Measurement, and Therapeutic Monitoring

This review will focus on our current state of understanding of the cellular and molecular mechanisms by which CsA exerts immunosuppression and will present new information on: pharmacokinetic variability of CsA, selection of specimen and method for measuring CsA concentration, identity of CsA metabolites and their immunosuppressive and toxic activity, and the relationship between steady-state pre-dose concen-trations of CsA in blood and response to treatment in transplant patients. In 1970 Sandoz scientists, in the continuing search for new and better medicines, retrieved soil specimens from the high plains area of southern Norway, Hardangervidda. Cyclosporine (CsA) was subsequently isolated from a new fungus strain, Tolypocladium inflatum Gams (1), obtained from those soil samples. Borel et al. discovered the immu