EFFECT OF TOLCAPONE ON PLASMA AND STRIATAL APOMORPHINE DISPOSITION INRATS

THE influence of tolcapone, an inhibitor of catechol-O-methyl transfer ase, was evaluated on the disposition of apomorphine, a dopamine agoni st used to treat Parkinson's disease, to explain a previously observed increase of duration of the effect of apomorphine associated with tol capone. Sampling was performed in rats before and at different times a fter administration of apomorphine and following that of tolcapone or saline. Both in plasma and striatum, times to reach maximal concentrat ion and maximal concentrations did not significantly differ between th e two groups but the elimination half-life times and areas under the c urve were significantly greater following tolcapone treatment than in the saline group. These results show that tolcapone can increase plasm a apomorphine bioavailability by modifying its liver catabolism.