Pharmacokinetics of nefiracetam and three metabolites in humans and stereoselective hydroxylation of its pyrrolidine ring

Xenobiotica. 1993 Jan;23(1):61-70. doi: 10.3109/00498259309059362.

Abstract

1. The kinetics of nefiracetam (I) and three metabolites (II-IV) were investigated in healthy volunteers. Compounds I-IV in serum and urine were measured by h.p.l.c. 2. After a single 200 mg dose of nefiracetam the drug was absorbed rapidly and showed peak serum levels of 16.3 +/- 0.9 nmol/ml. Cmax values of the three metabolites were comparatively low (0.96-4.89 nmol/ml), and tmax and t1/2 values of the metabolites (4.1-9.6 h and 7.8-21.9 h, respectively) were longer than those of I (1.6 h and 3.9 h respectively). Urinary excretion of I in 24 h was about 5% of the dose. The major urinary metabolite, a pyrrolidine ring scission product (IV), had a mean total excretion of 17.8% dose. The total of all four compounds in urine amounted to 43.4% dose. 3. In a multiple-dose study (daily 3 x 200 mg doses of nefiracetam for 7 days), the serum concentration profile of each compound indicated that the steady state was reached in 7 days. 4. Metabolite II existed as a racemate and III mainly as the (-)-enantiomer in human urine.

MeSH terms

  • Adult
  • Drug Administration Schedule
  • Humans
  • Hydroxylation
  • Male
  • Mixed Function Oxygenases / metabolism
  • Psychotropic Drugs / chemistry
  • Psychotropic Drugs / pharmacokinetics*
  • Psychotropic Drugs / urine
  • Pyrrolidines / metabolism
  • Pyrrolidinones / chemistry
  • Pyrrolidinones / pharmacokinetics*
  • Pyrrolidinones / urine
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • Psychotropic Drugs
  • Pyrrolidines
  • Pyrrolidinones
  • nefiracetam
  • Mixed Function Oxygenases