Relationship between pharmacokinetics and pharmacodynamics of calcineurin inhibitors in renal transplant patients.
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.
['Albring|Antje|A|', 'Wendt|Laura|L|', 'Harz|Nino|N|', 'Engler|Harald|H|', 'Wilde|Benjamin|B|', 'Kribben|Andreas|A|', 'Lindemann|Monika|M|', 'Schedlowski|Manfred|M|', 'Witzke|Oliver|O|']
D065095:Calcineurin Inhibitors D016572:Cyclosporine D016903:Drug Monitoring D005260:Female D005500:Follow-Up Studies D005919:Glomerular Filtration Rate D006084:Graft Rejection D006085:Graft Survival D006801:Humans D007166:Immunosuppressive Agents D007676:Kidney Failure, Chronic D007677:Kidney Function Tests D016030:Kidney Transplantation D008297:Male D008875:Middle Aged D009173:Mycophenolic Acid D011183:Postoperative Complications D011379:Prognosis D012307:Risk Factors D016559:Tacrolimus D014018:Tissue Distribution
pharmacokinetic pharmacodynamic calcineurin inhibitors renal transplantation cyclosporine A tacrolimus