Lack of an effect of Madopar on the disposition of tolcapone and its 3-O-methylated metabolite in rats.
The effect of Madopar (benserazide and L-dopa, 1:4) on the disposition of the new selective inhibitor of catechol-O-methyltransferase, tolcapone, in rats was investigated. There was no statistically significant difference in the pharmacokinetic parameters of tolcapone in the presence or absence of Madopar except for a change in the mean residence time after oral administration. Thus, we rejected the hypothesis that the consumption of S-adenyl-L-methionine by Madopar would change the disposition of tolcapone. There were no statistically significant differences in the cumulative amount absorbed of drug and the absorption rate in the presence or absence of Madopar. We concluded that there was no interaction between tolcapone and Madopar.
Funaki
T
T
Nippon Roche Research Center, Kanagawa, Japan.
Onodera
H
H
Ushiyama
N
N
Tsukamoto
Y
Y
Tagami
C
C
Fukazawa
H
H
Kuruma
I
I
D000818:Animals; D001545:Benserazide / Q000494:pharmacology*; D001577:Benzophenones / Q000493:pharmacokinetics*; D001711:Biotransformation; D065098:Catechol O-Methyltransferase Inhibitors; D004338:Drug Combinations; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006207:Half-Life; D007275:Injections, Intravenous; D007980:Levodopa / Q000494:pharmacology*; D008297:Male; D008745:Methylation; D009596:Nitrophenols; D051381:Rats; D017207:Rats, Sprague-Dawley; D012436:S-Adenosylmethionine / Q000493:pharmacokinetics; D014018:Tissue Distribution; D000077867:Tolcapone
D001577:Benzophenones; D065098:Catechol O-Methyltransferase Inhibitors; D004338:Drug Combinations; D004791:Enzyme Inhibitors; D009596:Nitrophenols; C005177:benserazide, levodopa drug combination; D007980:Levodopa; D001545:Benserazide; D012436:S-Adenosylmethionine; D000077867:Tolcapone