title: Effects of itraconazole and tandospirone on the pharmacokinetics of perospirone.
abstract: Perospirone is an atypical antipsychotic agent originated and clinically used in Japan. Based on an in vitro study, it is reported that perospirone is mainly metabolized to ID-15036 by cytochrome P450 (CYP) 3A4. In this study, the authors investigated the effects of itraconazole, which is a specific inhibitor of CYP3A4, or tandospirone, which is mainly metabolized by CYP3A4 and is expected to competitively inhibit the activity of this enzyme, on single oral dose pharmacokinetics of perospirone. After pretreatment with 200 mg daily of itraconazole or 10 mg daily of tandospirone for 5 days, 9 healthy male subjects received 8 mg of perospirone. Plasma concentrations of perospirone and ID-15036 up to 10 hours after perospirone dosing were measured by high-performance liquid chromatography (HPLC). The metabolism of perospirone was significantly inhibited by treatment with itraconazole but not by tandospirone. The present study suggests that CYP3A4 is significantly involved in metabolism of perospirone in humans.
authors.affiliation: Department of Psychiatry, Hokkaido University Graduate School of Medicine, Sapporo, Japan. masui@med.hokudai.ac.jp
authors.forename: Takuya
authors.initials: T
authors.lastname: Masui
authors.forename: Ichiro
authors.initials: I
authors.lastname: Kusumi
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Koyama
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D000935:Antifungal Agents / Q000494:pharmacology*; D014150:Antipsychotic Agents / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D019540:Area Under Curve; D051544:Cytochrome P-450 CYP3A; D065607:Cytochrome P-450 Enzyme Inhibitors; D004347:Drug Interactions; D006207:Half-Life; D006801:Humans; D007211:Indoles / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D054833:Isoindoles; D017964:Itraconazole / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013844:Thiazoles / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*
chemical_list: D000935:Antifungal Agents; D014150:Antipsychotic Agents; D065607:Cytochrome P-450 Enzyme Inhibitors; D007211:Indoles; D054833:Isoindoles; D010879:Piperazines; D011743:Pyrimidines; D017366:Serotonin Receptor Agonists; D013844:Thiazoles; C055267:tandospirone; D017964:Itraconazole; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; C065533:perospirone