title: Relationship between pharmacokinetics and pharmacodynamics of calcineurin inhibitors in renal transplant patients.
abstract: The calcineurin inhibitors (CNIs) cyclosporine A (CsA) and tacrolimus (Tac) are immunosuppressive drugs, which are typically employed in the field of organ transplantation. Both drugs have narrow therapeutic indices, highly variable pharmacokinetics, and are associated with severe adverse effects. In current clinical routine, the dose finding of CNIs is based on the measurement of their blood concentrations. However, this method is limited in its ability to determine the biological impact of the drug. Alternative monitoring strategies, focusing on the pharmacodynamics of CNIs, could help to personalize drug dosing and optimize the treatment with CNIs. Therefore, we analyzed the relationship between pharmacokinetic and pharmacodynamic of the CNIs CsA (n = 9) and Tac (n = 8) in stable renal transplant patients during a 12-h dosing period. We observed a significant decrease in the drug-blood concentration during the course of the day and in parallel a significant recovery of T cell function. In addition, our data document that analysis of intracellular interleukin (IL)-2 production and determination of the IL-2 release are accurate parameters for monitoring the pharmacodynamics of CNIs.
authors.affiliation: Institute of Medical Psychology and Behavioral Immunobiology, University Hospital Essen, Essen, Germany.
authors.forename: Antje
authors.initials: A
authors.lastname: Albring
authors.forename: Laura
authors.initials: L
authors.lastname: Wendt
authors.forename: Nino
authors.initials: N
authors.lastname: Harz
authors.forename: Harald
authors.initials: H
authors.lastname: Engler
authors.forename: Benjamin
authors.initials: B
authors.lastname: Wilde
authors.forename: Andreas
authors.initials: A
authors.lastname: Kribben
authors.forename: Monika
authors.initials: M
authors.lastname: Lindemann
authors.forename: Manfred
authors.initials: M
authors.lastname: Schedlowski
authors.forename: Oliver
authors.initials: O
authors.lastname: Witzke
mesh_terms: D065095:Calcineurin Inhibitors / Q000493:pharmacokinetics* / Q000494:pharmacology*; D016572:Cyclosporine / Q000493:pharmacokinetics / Q000494:pharmacology; D016903:Drug Monitoring; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D006084:Graft Rejection / Q000517:prevention & control*; D006085:Graft Survival; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007676:Kidney Failure, Chronic / Q000601:surgery*; D007677:Kidney Function Tests; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000493:pharmacokinetics / Q000494:pharmacology; D011183:Postoperative Complications; D011379:Prognosis; D012307:Risk Factors; D016559:Tacrolimus / Q000493:pharmacokinetics / Q000494:pharmacology; D014018:Tissue Distribution
chemical_list: D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D009173:Mycophenolic Acid; D016559:Tacrolimus
keywords: calcineurin inhibitors; cyclosporine A; pharmacodynamic; pharmacokinetic; renal transplantation; tacrolimus