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

The effect of food on the pharmacokinetics and tolerability of cabergoline in man was investigated. For this purpose an open, randomized, single-dose study was conducted in 12 healthy male volunteers who received 1 mg cabergoline as tablets both under fasting conditions and after a breakfast containing a substantial amount of carbohydrates, fat, and 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 168 h respectively after administration and cabergoline concentration was measured in both fluids using a validated radioimmunoassay. Tolerability assessment included haematology, blood chemistry, and urinalysis, blood pressure and heart rate measurements, and ECG. Under both fasting and fed conditions low but persistent cabergoline plasma levels 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 conditions, Cmax values averaged 44 and 54 pg mL−1, AUC(0–336 h) averaged 6392 and 5331 pg h mL−1, Ae(0–168 h) averaged 12·7 and 11·9 μg, and t1/2 averaged 109·7 and 101·3 h, respectively. No statistically significant difference was found when Cmax, AUC(0–336 h), t1/2, and Ae(0–168 h) from subjects treated under fasting and fed conditions were compared. Median tmax values in subjects treated under fasting or fed conditions were identical (2·5 h). The statistical analysis applied to the parameters chosen to evaluate the variations in the blood pressure profiles observed either supine or standing did not show any significant difference between the fed and fasting conditions. Heart rate values were not significantly modified after cabergoline under either fed or fasting conditions. Laboratory evaluation showed some minor deviations from normal, which were not clinically relevant (only one subject showed an occasional and transient elevation in alkaline phosphatase which disappeared in the subsequent laboratory evaluations) and were considered for the most part not to be drug related. Eleven subjects reported adverse events (one after both treatments, five only after drug intake under fasting conditions, and five only after drug intake with food). Side-effects, typical of the pharmacological class, included headache, somnolence, dizziness, nausea, light-headedness, feeling of faintness, and slowing of thought. They were reported mostly on the day of the first drug administration, were mainly short lasting, and were all mild or moderate in severity. In conclusion, the comparison of the pharmacokinetic and tolerability parameters evaluated in the present study indicates that the pharmacokinetics, as well as the safety, of cabergoline are not modified by food intake.