Cyclosporine Concentration Determinations for Monitoring and Pharmacokinetic Studies

Abstract

The availability of the immunosuppressant cyclosporin has led to significant improvements in the recent success of clinical organ transplantation. Problems associated with cyclosporine therapy include serious adverse reactions, such as nephrotoxicity, wide variability in the drug's pharmacokinetics, and several complex drug interactions. Monitoring of drug concentrations is accepted as a part of the routine care of patients receiving cyclosporine. However, cyclosporine concentrations can be determined in different biologic fluids by either radioimmunoassay or high-performance liquid chromatographic techniques. Controversy exists regarding the optimal analytic technique to be used for cyclosporine monitoring and pharmacokinetic studies. This commentary addresses factors including: why the monitoring of cyclosporine concentrations is important, the differences between the biologic fluids and analytic techniques, when monitoring and special pharmacokinetic studies are indicated, what some major transplant centers have established as a "therapeutic range" for cyclosporine concentrations, and provides guidelines for the optimal clinical monitoring of cyclosporine concentrations.

Synergism between long-acting bromocryptine microcapsules and cyclosporine A in the prevention of various autoimmune diseases in rats

“…Our data suggest an association between the delay in DMonset observed with the combination therapy (CsA plus CBLA) and a transient increase in CsA bioavailability. Acute increase of CsA in blood has been reported after co-administration with ketoconazole, erythromycin or cimetidine, which all interfere with the hepatic microsomal cytochrome P-450 activity [27,28]. In humans, both bromocryptine and CsA compete as substrates of cytochrome P-450 3A [29].…”

Transplant Pharmacy: 30 Years of Improving Patient Care

“…Cyclosporine and tacrolimus were uniquely difficult drugs to manage, and pharmacy provided research into pharmacokinetics, 2-4 drug interactions, 5-7 metabolites, 8,9 and therapeutic drug monitoring. 10, 11 More recently, pharmacy has been able to document ways to improve patient adherence, 12-15 improve blood pressure control, 14 provide economically sound drug therapy, 16, 17 and provide patient education on their medications. 18,19…”

Dose dependent absorption and linear disposition of cyclosporin A in rat

“…In the morning the current solution of CyA was given to the rat as a 4 h constant-rate (0.5 ml min-l) infusion (calibrated pump model 355, Sage Instruments, Cambridge, Mass., USA) via the jugular vein catheter. Blood samples were taken via the arterial catheter 2,4,5,7,9,10,12,24,30,34,36, and 48 h after CyA administration. Replacement volumes of physiological saline were administered via the catheter to maintain haemodynamics.…”