Effect of tolcapone on plasma and striatal apomorphine disposition in rats.
The influence of tolcapone, an inhibitor of catechol-O-methyl transferase, was evaluated on the disposition of apomorphine, a dopamine agonist used to treat Parkinson's disease, to explain a previously observed increase of duration of the effect of apomorphine associated with tolcapone. Sampling was performed in rats before and at different times after administration of apomorphine and following that of tolcapone or saline. Both in plasma and striatum, times to reach maximal-concentration and maximal concentrations did not significantly differ between the two groups but the elimination half-life times and areas under the curve were significantly greater following tolcapone treatment than in the saline group. These results show that tolcapone can increase plasma apomorphine bioavailability by modifying its liver catabolism.
Coudoré
F
F
Equipe NeuroPsychoPharmacologie Université d'Auvergne, Laboratoires de Pharmacologie, Faculté de Pharmacie, Clermont-Ferrand, France.
Durif
F
F
Duroux
E
E
Eschalier
A
A
Fialip
J
J
D000818:Animals; D000978:Antiparkinson Agents / Q000097:blood / Q000493:pharmacokinetics*; D001058:Apomorphine / Q000097:blood / Q000493:pharmacokinetics*; D001577:Benzophenones / Q000494:pharmacology*; D003342:Corpus Striatum / Q000378:metabolism*; D006207:Half-Life; D008297:Male; D008657:Metabolic Clearance Rate; D009596:Nitrophenols; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution; D000077867:Tolcapone
D000978:Antiparkinson Agents; D001577:Benzophenones; D009596:Nitrophenols; D000077867:Tolcapone; D001058:Apomorphine