PHARMACODYNAMICS AND RELATIVE BIOAVAILABILITY OF CABERGOLINE TABLETS VS SOLUTION IN HEALTHY-VOLUNTEERS

The effect of formulation on the urinary pharmacokinetics, pharmacodyn amics, and relative bioavailability of cabergoline was investigated. T welve healthy female volunteers, aged 23-35 years, were treated, accor ding to an open, randomized, crossover design, with cabergoline (l-mg single oral dose) both as tablets and as a solution. The two administr ations were separated by a 4-week wash-out period. Cabergoline and pro lactin were measured in urine and plasma, respectively, by specific ra dioimmunoassays. Blood samples were collected before and up to 30 days after dosing. Urine was collected before and up to 8 days after dosin g. Cabergoline elimination half-lives calculated from urinary data wer e 68 and 63 h after administration of the tablets and the solution, re spectively. Urinary excretion of unchanged cabergoline accounted, on a verage, for 1.92% (range, 0.14-3.26) and 1.80% (range, 0.67-3.09) of t he dose after administration of the tablets and the aqueous solution, respectively. Relative bioavailability of tablets vs solution was 99% (geometric mean with the 90% confidence intervals of 68-144%). Prolact in levels in 10 out of 12 subjects fell below the detection limit of t he assay (1.5 mu g/L) after both treatments. The mean maximum prolacti n decrease (ca. 70%) was achieved by 2 or 3 h after dosing; the effect persisted up to 9 days, being completely exhausted 23-28 days after d osing. The analysis of variance performed on the pharmacodynamic effec ts of the two cabergoline formulations indicated that the percent decr eases of plasma prolactin levels were not significantly different for tablets and solution. These results indicate that the pharmacodynamics and relative bioavailability of cabergoline are not influenced by for mulation, as tablets or solution.