THE EFFECT OF FOOD AND BILE-ACID ADMINISTRATION ON THE RELATIVE BIOAVAILABILITY OF CYCLOSPORINE

1. The relative bioavailability of cyclosporin was studied in 11 healthy volunteers after single oral capsule doses of cyclosporin on three separate occasions; fasting, with breakfast and with breakfast together with bile acid tablets (400 mg of cholic acid and 100 mg of dehydrocholic acid). 2. There was a significant increase in the area under the blood concentration vs time curve (AUC) of cyclosporin when the drug was taken together with breakfast and bile acid tablets (9078 ng ml‐1 h) as compared with breakfast alone (7453 ng ml‐1 h, P less than 0.05) or fasting conditions (7283 ng ml‐1 h, P less than 0.01). 3. A blood drug concentration vs time curve displaying two peaks was present in 9/11 subjects when cyclosporin was taken with breakfast or with breakfast and bile acid tablets, but only one peak was present when cyclosporin was taken during fasting, suggesting an enterohepatic circulation of cyclosporin or a second absorption phase after the meal. 4. In a separate study, 12 h trough blood cyclosporin concentrations were measured before and after 1 week of bile acid treatment in 19 clinically stable, out‐patient transplant recipients who were treated with oral cyclosporin solution (mean dose 2.0 mg kg‐1 twice daily). The administration of cyclosporin was not standardized with regard to food intake. There was no significant difference in the blood concentrations of cyclosporin before and after bile acid treatment (114 +/− 38 ng ml‐1 vs 121 +/− 38 ng ml‐1).(ABSTRACT TRUNCATED AT 250 WORDS) 1990 The British Pharmacological Society