Pharmacokinetics of cyclosporin A

Abstract

What distinguishes cyclosporin A (CsA) from other medications (e.g. beta-blockers) whose pharmacokinetics are of interest only to a specialized group of clinical pharmacologists and not to the medical profession at large who prescribe these drugs on a daily basis? Why is it that one can claim rightfully that the proper therapeutic use of CsA requires an understanding and appreciation of its pharmacokinetics? The answer is simple: standard dosing regimens of CsA do not work because the therapeutic range of CsA is narrow and the variability of its dose—concentration relationship (i.e. pharmacokinetics) is large between different patients and within an individual patient. This predicament leaves the physician only two choices: (l) he uses standardized, but subtherapeutic, doses of CsA, and he substitutes with therapeutic doses of other conventional immunosuppressive medications (azathioprine, anti-lymphocyte globulin), thus exploiting a putatively synergistic effect of CsA; or (2) he individualizes the CsA dose for each patient by strictly monitoring CsA blood concentrations. The latter approach can be applied successfully only when the pharmacokinetic properties of CsA are taken into account. It is self-evident that this chapter will appeal only to those who try to exploit the uniquely selective effects of CsA by prescribing it in therapeutic doses as the cornerstone of their immunomodulating strategy.