Prevention of kidney graft rejection with cyclosporine leads to a large interindividual pharmacokinetic variability. However, food intake is likely to alter cyclosporine pharmacokinetics, and therefore its efficacy. The aim of our study was to evaluate the influence of food and lipid intake on cyclosporine pharmacokinetics. Twenty-four kidney grafted patients treated with Neoral® were included in this prospective monocentric study. In all patients, the pharmacokinetics of cyclosporine was evaluated in two occasions, after meal ('feed') and without meal ('fasting'). At each occasion, blood samples were collected at trough, and 0.5, 1, 2, 3, and 4 h after administration. Cyclosporine pharmacokinetics was described using a Bayesian pharmacokinetic model including two-compartments with first-order transfer and elimination rate constants, and a gamma absorption model. Influence of meal or olive oil, very common in Morocco, was tested as covariates on interoccasion variability parameters. Cyclosporine concentration-time data were satisfactorily described using the Bayesian pharmacokinetic model. Food intake significantly increased volume of distribution and decreased elimination of cyclosporine. The influence of oil intake explained a large part of this effect, suggesting that lipid intake was the main factor of pharmacokinetic variability due to food. This intake resulted in a decrease in area under the concentration curve between two administrations of 14.6%. Food, and especially lipid intake is likely to decrease the exposure to cyclosporine and may therefore lead to a decrease in treatment efficacy. Therefore, to ensure optimal immunosuppression in time, meal composition should remain as steady as possible.
Keywords: cyclosporine; food intake; kidney transplantation; pharmacokinetics.
© 2020 Société Française de Pharmacologie et de Thérapeutique.