Cytochrome P450 3A inhibitor itraconazole affects plasma concentrations of risperidone and 9-hydroxyrisperidone in schizophrenic patients

• Published in: Clinical pharmacology and therapeutics 2005-11, Vol.78 (5), p.520-528
• Main Authors: Jung, Sun Min, Kim, Kyoung‐Ah, Cho, Hyun‐Kee, Jung, Il Geun, Park, Pil‐Whan, Byun, Won Tan, Park, Ji‐Young
• Format: Article
• Language: English
• Subjects: Adult; Antifungal Agents - adverse effects; Antipsychotic Agents - pharmacokinetics; Antipsychotic Agents - therapeutic use; Biological and medical sciences; Chromatography, High Pressure Liquid; Cytochrome P-450 CYP3A - genetics; Cytochrome P-450 CYP3A Inhibitors; Dose-Response Relationship, Drug; Drug Interactions; Enzyme Inhibitors - adverse effects; Female; Genotype; Half-Life; Humans; Isoxazoles - blood; Itraconazole - adverse effects; Male; Medical sciences; Middle Aged; Paliperidone Palmitate; Pharmacology. Drug treatments; Psychiatric Status Rating Scales; Pyrimidines - blood; Risperidone - blood; Risperidone - therapeutic use; Schizophrenia - blood; Schizophrenia - drug therapy
• ISSN: 0009-9236; 1532-6535
• DOI: 10.1016/j.clpt.2005.07.007

Background and Objective Despite the belief that cytochrome P450 (CYP) 2D6 alone is responsible for the metabolism of risperidone, several studies suggest that CYP3A may be involved. The aim of this study was to evaluate the effect of itraconazole, a CYP3A inhibitor, on the plasma concentrations of risperidone and 9‐hydroxyrisperidone in schizophrenic patients in relation to CYP2D6 genotype. Methods Nineteen schizophrenic patients treated with 2 to 8 mg/d of risperidone received 200 mg/d of itraconazole for a week. Plasma concentrations of risperidone and 9‐hydroxyrisperidone were measured immediately before and after itraconazole treatment, as well as at 1 week after itraconazole treatment was stopped, together with clinical assessment by use of the Udvalg for Kliniske Undersøgelser Side Effect Rating Scale and the Brief Psychiatric Rating Scale. Results Dose‐normalized plasma concentrations of risperidone and 9‐hydroxyrisperidone before itraconazole treatment (0.9 ± 0.8 ng · mL−1 · mg−1 and 6.9 ± 3.3 ng · mL−1 · mg−1, respectively) were significantly elevated after itraconazole treatment (1.6 ± 1.3 ng · mL−1 · mg−1 and 11.3 ± 4.5 ng · mL−1 · mg−1) and decreased 1 week after its discontinuation (1.0 ± 0.8 ng · mL−1 · mg−1 and 7.2 ± 3.7 ng · mL−1 · mg−1) (P .05). Itraconazole increased the concentrations of risperidone by 69% (P