EFFECT OF DIETARY-FAT ON THE PHARMACOKINETICS AND PHARMACODYNAMICS OF CYCLOSPORINE IN KIDNEY-TRANSPLANT RECIPIENTS

Objective: To investigate the effect of dietary fat on the pharmacokinetics and pharmacodynamics of cyclosporine. Methods: Sixteen stable kidney transplants recipients (mean age, 50.4 years; age range, 19 to 63 years; six women) who were maintained on oral cyclosporine therapy were randomized to receive a high- or lowfat diet for periods of 7 days in a balanced crossover study. The crossover was separated by a 7-day washout period, when the usual diet was followed. Oral cyclosporine was taken once daily with breakfast. Twenty-four-hour pharmacokinetic studies were conducted during each dietary period on day 6 after oral cyclosporine and on day 7 after a 3-hour intravenous cyclosporine infusion (30% of oral dose). Sequential blood samples were also taken after the oral dose on day 6 for lymphocyte transformation studies. Results: The mean breakfast fat intake and total daily fat intake were 6.5 and 5.5 times higher, respectively, during the high-fat diet than during the low-fat diet. The bioavailability and clearance of cyclo-sporine were found to be significantly higher during the high-fat diet p = 0.02 and p = 0.01, respectively). As a consequence, the area under the blood concentration-time curve (AUG) after the oral dose was not significantly different between the two diets, There were no significant differences in concanavalin A-stimulated proliferation of peripheral blood lymphocytes between the high- and low-fat diets. Conclusions: An increased fat content of food significantly increases cyclosporine bioavailability and clearance. However, this is unlikely to be of clinical importance during oral administration because the AUC and pharmacodynamics of cyclosporine are not affected significantly.