The effects of calcineurin inhibitors on prostanoid synthesis: a randomised cross-over study in healthy humans.
Ozbay L.A, Stubbe J, et al.Transplant International 2013; 26: 131-137.
Aims
Cyclosporine (CsA) and Tacrolimus (Tac) are both calcineurin inhibitors implicated in post-transplant complications including cardiovascular morbidity. The study compares the effects of CsA and Tac concentrations on prostanoid synthesis in healthy humans.
Interventions
Infusion of CsA, Tac or saline; at t=0 min, bolus doses of CsA (0.34 mg/kg), Tac (0.0024 mg/kg) or saline were infused, followed by maintenance doses of CsA (0.155mg/kg/h), Tac (0.0012 mg/kg/h), or saline until t=285 mins.
Participants
10 healthy men. Women were excluded from the study.
Outcomes
Concentration of prostanoids in plasma and urine; basal PGIâ‚‚ metabolite levels, basal levels of thromboxane in the urine, COX1 and COX-2 activity, glucose metabolism, systolic and diastolic blood pressure and levels of calcineurin inhibitors.
Follow-up
285 minutes after the start of the infusion.
CET Conclusions
In this double blind crossover study the effect of 5 hour infusions of cyclosporine, tacrolimus and saline were studied with respect to their effect on prostanoids. 10 health male volunteers were used in the study and it appeared that clinically relevant doses of cyclosporine A and tacrolimus produced different changes in prostanoid levels in healthy human subjects, for cyclosporine suppresses COX-2 activity while tacrolimus decreases platelet activity.
Data analysis
Per protocol analysis
Trial registration
ClinicalTrials.gov - NCT00766909