Single- and multiple-dose pharmacokinetics of nefiracetam, a new nootropic agent, in healthy volunteers.
The pharmacokinetic profile of nefiracetam (N-(2,6-dimethylphenyl)-2-(2-oxo-1-pyrrolidinyl)acetamide), a new nootropic agent, was studied in healthy Japanese male volunteers. Nefiracetam was administered orally at doses of 10-200 mg in the single-dose studies, and at doses of 200 mg three times a day for seven days in the multiple-dose study. An HPLC method was used to determine the concentrations of nefiracetam in serum, urine and faecal samples. Linear kinetic behaviour was obtained after single oral administration. Serum concentrations of nefiracetam reached maximum values (Cmax) within 2 h for all dosage groups, and declined monophasically after Cmax with half-lives of 3-5 h. The area under the concentration-time curve (AUC infinity) and Cmax were linearly related to the dose. The apparent clearance (CL) values were 94.4-140.3 mL min-1. Urinary excretion of nefiracetam was independent of the administered dose, and less than 10% of the dose was recovered in urine as the unchanged form within 24 h after administration. Renal clearance (CLR) did not change significantly as dose increased from 10 to 1200 mg. Faecal excretion of nefiracetam was less than 0.1% of the dose up to 24 h after a 300 mg oral dose. Food intake delayed the absorption of nefiracetam but did not significantly modify its pharmacokinetics. No clinically significant accumulation of nefiracetam in the body was observed during and after multiple doses.
Fujimaki
Y
Y
Drug Metabolism and Analytical Chemistry Research Center, Daiichi Pharmaceutical Co. Ltd, Tokyo, Japan.
Sudo
K
K
Hakusui
H
H
Tachizawa
H
H
Murasaki
M
M
D000284:Administration, Oral; D000328:Adult; D001682:Biological Availability; D005243:Feces / Q000737:chemistry; D006207:Half-Life; D006801:Humans; D008297:Male; D008875:Middle Aged; D011619:Psychotropic Drugs / Q000494:pharmacology*; D011760:Pyrrolidinones / Q000008:administration & dosage / Q000493:pharmacokinetics*
D011619:Psychotropic Drugs; D011760:Pyrrolidinones; C058876:nefiracetam