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 (pramipexole, ropinirole, pergolide, and bromocriptine) on six human cytochrome P450 enzyme activities were evaluated using a simple in vitro inhibition screen. Drug-P450 interactions characterized as potent (i.e. greater than 50% inhibition of control enzyme activity) were then further examined to determine an IC50 for the interaction. Of the dopamine receptor agonists tested, three drugs, ropinirole, pergolide, and bromocriptine, were found to inhibit the activity of at least one human cytochrome P450 enzyme, while the remaining dopamine agonist, pramipexole, was devoid of any potent P450 interaction. None of the agonists tested inhibited the P450 marker activities of 2C9, 2C19, and 2E1. However, partial inhibition was observed between ropinirole and CYP1A2 and pergolide and CYP3A4. In contrast, potent interactions were observed between CYP2D6 and pergolide and ropinirole, as well as with CYP3A4 and bromocriptine. The results of this study indicate several drug P450 interactions; however, the likelihood of an in vivo interaction with these drugs remains to be established.
Wynalda
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Drug Metabolism Research, Pharmacia & Upjohn, Kalamazoo, MI 49007, USA.
Wienkers
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D052160:Benzothiazoles; D001971:Bromocriptine / Q000494:pharmacology; D065607:Cytochrome P-450 Enzyme Inhibitors; D018491:Dopamine Agonists / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D010479:Pergolide / Q000494:pharmacology; D000077487:Pramipexole; D013844:Thiazoles / Q000494:pharmacology
D052160:Benzothiazoles; D065607:Cytochrome P-450 Enzyme Inhibitors; D018491:Dopamine Agonists; D004791:Enzyme Inhibitors; D007211:Indoles; D013844:Thiazoles; C046649:ropinirole; D010479:Pergolide; D001971:Bromocriptine; D000077487:Pramipexole