Lack of an Effect of Madopar on the Disposition of Tolcapone and its 3-O-Methylated Metabolite in Rats

Abstract

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.

Pharmacokinetics and Pharmacodynamics of Entacapone and Tolcapone after Acute and Repeated Administration: A Comparative Study in the Rat

“…After intravenous administration of 10 mg/kg tolcapone, the t 1/2 was 0.9 h and total clearance 470 ml ϫ h Ϫ1 ϫ kg Ϫ1 . The oral bioavailability was 48% for 20 mg/kg and 56% for 40 mg/kg (Funaki et al, 1994(Funaki et al, , 1995. After administration of 5.7 mg/kg entacapone intravenously, the t 1/2 and total clearance were 0.4 h and 829 ml ϫ h Ϫ1 ϫ kg Ϫ1 , respectively.…”