Pharmacology and pharmacokinetics of cyclosporine

Cyclosporine (CsA) is a lipophilic, immunosuppressive peptide which selectively inhibits T-lymphocyte activation in response to antigen stimulation. Although it is the drug of choice in organ transplantation, its clinical use is hampered by toxicity and unpredictable pharmacokinetics. CsA absorption from the small intestine is normally incomplete and is further reduced by intestinal dysfunction and low bile flow. That which enters the systemic blood is metabolized almost entirely by the liver and excreted in the bile. Blood CsA levels are altered to a clinically relevant degree by abnormal liver function and by drugs that induce or inhibit hepatic metabolism. Intestinal absorption may also play a role in some drug interactions. The narrow therapeutic range of CsA and the various factors that alter its kinetics underlie the continuing need to monitor this drug in blood.