ASSESSMENT OF POTENTIAL INTERACTIONS BETWEEN DOPAMINE-RECEPTOR AGONISTS AND VARIOUS HUMAN CYTOCHROME-P450 ENZYMES USING A SIMPLE IN-VITRO INHIBITION SCREEN

The selectivity of inhibition for four dopamine receptor agonists (pra mipexole, ropinirole, pergolide, and bromocriptine) on six human cytoc hrome P450 enzyme activities were evaluated using a simple in vitro in hibition screen. Drug-P450 interactions characterized as potent (i.e. greater than 50% inhibition of control enzyme activity) were then furt her examined to determine an IC50 for the interaction. Of the dopamine receptor agonists tested, three drugs, ropinirole, pergolide, and bro mocriptine, were found to inhibit the activity of at least one human c ytochrome P450 enzyme, while the remaining dopamine agonist, pramipexo le, was devoid of any potent P450 interaction. None of the agonists te sted inhibited the P450 marker activities of 2C9, 2C19, and 2E1. Howev er, partial inhibition was observed between ropinirole and CYP1A2 and pergolide and CYP3A4. In contrast, potent interactions were observed b etween CYP2D6 and pergolide and ropinirole, as well as with CYP3A4 and bromocriptine. The results of this study indicate several drug P450 i nteractions; however, the likelihood of an in vivo interaction with th ese drugs remains to be established.