Cyclosporin A and its metabolites, distribution in blood and tissues.

Cyclosporin A (CsA), a non-myelotoxic immunosuppressant, and its metabolites are widely distributed in the body. Highest concentrations of CsA have been detected in the pancreas, adipose tissue and liver, lowest concentrations in brain, muscle, blood and other body fluids. Metabolites are distributed differently to CsA. In addition to lipid partition, intracellular binding to cyclophilin, a peptidyl-prolyl cis-trans isomerase, appears to play a role in its tissue distribution. The temperature dependence of such binding in erythrocytes poses difficulty in serum or plasma measurements. Tissue specific processes may also influence action and toxicity of CsA and its metabolites; thus, a better understanding of the complex distribution pattern of CsA and its metabolites would be important for establishing improved strategies and selection of appropriate specific methodologies for drug monitoring.