Advances in clinical determinants and mechanisms of calcineurin inhibitor pharmacokinetic disposition in vivo / 中国药理学通报

ABSTRACT

Tacrolimus and cyclosporine are both calcineurin inhibitors ( CNI) that widely used for immunosuppression and have the characteristics of great intra-and inter-variabilities in phar-macokinetics and pharmacodynamics.CNI undergoes extensive first-pass metabolism and is substrate for cytochrome P450 (CYP) 3A4, CYP3A5 and P-glycoprotein in intestine and liver.'Hie functions of the enzyme and transporter are determined by complex interactions including gene polymorphisms, induction or inhibition of drugs and endogenous substances ( such as inflam-matory factors).This review summarizes the clinical determinants of CNI treatment variability, including food intake, diarrhea and other intestinal diseases, anemia, hypoproteinemia, hyperlipidemia, liver and kidney disease and combination medications.The underlying mechanisms are also discussed.