THE EFFECT OF FOOD ON CABERGOLINE PHARMACOKINETICS AND TOLERABILITY IN HEALTHY-VOLUNTEERS

The effect of food on the pharmacokinetics and tolerability of cabergo line in man was investigated. For this purpose an open, randomized, si ngle-dose study was conducted in 12 healthy male volunteers who receiv ed 1 mg cabergoline as tablets both under fasting conditions and after a breakfast containing a substantial amount of carbohydrates, fat, an d proteins, in a crossover fashion. The two treatments were separated by a 4 week washout period. Plasma and urine were collected up to 336 and 168h respectively after administration and cabergoline concentrati on was measured in both fluids using a validated radioimmunoassay. Tol erability assessment included haematology, blood chemistry, and urinal ysis, blood pressure and heart rate measurements, and EGG. Under both fasting and fed conditions low but persistent cabergoline plasma level s were observed in the present study up to 2 weeks after drug intake, in agreement with the long-lasting prolactin-lowering activity of the drug. In subjects receiving cabergoline under fed or fasting condition s, C-max values averaged 44 and 54 pg mL(-1), AUC((0-336h)) averaged 6 392 and 5331 pg h mL(-1), Ae((0-168h)) averaged 12 . 7 and 11 . 9 mu g , and t(1/2) averaged 109 . 7 and 101 . 3h, respectively. No statistic ally significant difference was found when C-max, AUC((0-336h)), t(1/2 ), and Ae((0-168h)) from subjects treated under fasting and fed condit ions were compared. Median t(max) values in subjects treated under fas ting or fed conditions were identical (2 . 5h). The statistical analys is applied to the parameters chosen to evaluate the variations in the blood pressure profiles observed either supine or standing did not sho w any significant difference between the fed and fasting conditions. H eart rate values were not significantly modified after cabergoline und er either fed or fasting conditions. Laboratory evaluation showed some minor deviations from normal, which were not clinically relevant (onl y one subject showed an occasional and transient elevation in alkaline phosphatase which disappeared in the subsequent laboratory evaluation s) and were considered for the most part not to be drug related. Eleve n subjects reported adverse events (one after both treatments, five on ly after drug intake under fasting conditions, and five only after dru g intake with food). Side-effects, typical of the pharmacological clas s, included headache, somnolence, dizziness, nausea, light-headedness, feeling of faintness, and slowing of thought. They were reported most ly on the day of the first drug administration, were mainly short last ing, and were all mild or moderate in severity. In conclusion, the com parison of the pharmacokinetic and tolerability parameters evaluated i n the present study indicates that the pharmacokinetics, as well as th e safety, of cabergoline are not modified by food intake.