Effect of carbamazepine on the single oral dose pharmacokinetics of perospirone and its active metabolite

Prog Neuropsychopharmacol Biol Psychiatry. 2006 Sep 30;30(7):1330-3. doi: 10.1016/j.pnpbp.2006.02.012. Epub 2006 Apr 4.


Perospirone is a serotonin 5-HT(2A) and dopamine D(2) receptor antagonist which originated in Japan. It has been shown that perospirone is metabolized to ID-15036 mainly by CYP3A4 based on an in vitro study. To investigate the metabolism of perospirone in humans, the authors measured the concentration of perospirone and ID-15036 after a single oral dose of perospirone (8 mg) in 10 healthy male subjects, before and during coadministration of carbamazepine, known as a potent inducer of CYP3A4. Before carbamazepine coadministration, the peak plasma concentrations+/-SD of perospirone and ID-15036 were 4.0+/-4.3 and 11.7+/-7.1 ng/ml, respectively. During carbamazepine coadministration, the concentration of perospirone was decreased below the detection limit, and that of ID-15036 was 6.0+/-1.7 ng/ml. The concentrations of perospirone and ID-15036 were influenced significantly by the treatment with carbamazepine, and this was probably attributable to the induction of CYP3A4. This study provided an in vivo evidence of involvement of CYP3A4 in the metabolism of perospirone.

Publication types

  • Clinical Trial
  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Anticonvulsants / administration & dosage*
  • Antipsychotic Agents / blood
  • Antipsychotic Agents / pharmacokinetics*
  • Carbamazepine / administration & dosage*
  • Chromatography, High Pressure Liquid
  • Cytochrome P-450 CYP3A
  • Cytochrome P-450 Enzyme System / metabolism*
  • Drug Interactions
  • Enzyme Activation / drug effects
  • Humans
  • Immunoenzyme Techniques / methods
  • Indoles / administration & dosage
  • Indoles / blood*
  • Indoles / pharmacokinetics*
  • Isoindoles
  • Male
  • Middle Aged
  • Prolactin / blood
  • Thiazoles / administration & dosage
  • Thiazoles / blood*
  • Thiazoles / pharmacokinetics*


  • Anticonvulsants
  • Antipsychotic Agents
  • Indoles
  • Isoindoles
  • Thiazoles
  • hydroxyperospirone
  • Carbamazepine
  • Prolactin
  • Cytochrome P-450 Enzyme System
  • Cytochrome P-450 CYP3A
  • CYP3A4 protein, human
  • perospirone