High-fat meals increase the clearance of cyclosporine

High-fat meals increase the clearance and volume of distribution, but not the mean residence time, of cyclosporine in seven healthy volunteers when either plasma or blood analyses are used. This unexpected finding for a low-extraction ratio drug should not be explainable in terms of increased blood flow. We hypothesize that dietary fat can act as a carrier for cyclosporine and enhance both its volume of distribution and its clearance. We suggest that clearance then occurs following metabolism of lipids due to lipase activity within the hepatocyte, thereby releasing free drug for metabolism.