Comparative pharmacokinetics of sulpiride and N-[(1-butyl-2-pyrrolidinyl)methyl]-2-methyl-5-sulfamoyl-2,3- dihydrobenzofuran-7-carboxamide hydrochloride, a new lipophilic substituted benzamide in rats.
The pharmacokinetics of a new lipophilic substituted benzamide N-[(1-butyl-2-pyrrolidinyl)methyl]-2-methyl-5-sulfamoyl-2,3- dihydrobenzofuran-7-carboxamide hydrochloride (1) and sulpiride in both plasma and brain were investigated in rats. The octanol-water partition coefficients of the base of 1(2) and sulpiride were 6.3 and 0.2, respectively. The eliminations of 2 from plasma and brain were similar to those of sulpiride. The systemic bioavailabilities of 1 and sulpiride after oral administration of 200 mg/kg were 60.9 +/- 10.9 and 18.2 +/- 6.4%, respectively. The brain concentrations of 2 were about 2-3 times higher than those of sulpiride until 4 h after oral administration of 100 mg/kg. The brain/plasma ratios of 2 were about 2 times higher than those of sulpiride. These results indicate that the penetration of 2 through the gastrointestinal membrane and/or the blood-brain barrier are higher than those of sulpiride.
Yamada
I
I
Research Laboratories, Yoshitomi Pharmaceutical Industries Ltd., Fukuoka, Japan.
Mizuta
H
H
Ogawa
K
K
Tahara
T
T
D000818:Animals; D014151:Anti-Anxiety Agents / Q000493:pharmacokinetics*; D001572:Benzofurans / Q000493:pharmacokinetics*; D008297:Male; D011759:Pyrrolidines / Q000493:pharmacokinetics*; D051381:Rats; D011919:Rats, Inbred Strains; D013469:Sulpiride / Q000493:pharmacokinetics*
D014151:Anti-Anxiety Agents; D001572:Benzofurans; D011759:Pyrrolidines; C062632:Y 20024; D013469:Sulpiride