Comparison of plasma levels between oral solution and fine granule dosage forms of risperidone

Abstract

Objective. In Japan, there are several clinical reports that risperidone (RIS) oral solution (OS) requires shorter time for tranquilization and induces fewer extrapyramidal symptoms (EPS) than other dosage forms; i.e. fine granules (FG). Our aim is to compare plasma levels of RIS, its active metabolite (9-OH-RIS), and their sum (active moiety; AM) between RIS-OS and RIS-FG in a multiple-dose regimen. Method. A 12-week cross-over study was conducted in nine patients with schizophrenia treated with 3 mg of RIS twice daily. The study period was divided into four terms, each term being 3 weeks. RIS-FG and RIS-OS were given in two alternate terms each. Blood samples were collected on the last day of each term just before and at 1 h after RIS treatment to measure plasma levels of RIS, 9-OH-RIS, and prolactin. Result. Plasma levels of RIS, 9-OH-RIS, AM, and prolactin before treatment were significantly lower for RIS-OS than for RIS-FG, while no significant difference was observed between the two forms at 1 h after administration. Conclusion. In a multiple-dose regimen, RIS-OS treatment caused a larger diurnal fluctuation in plasma level of AM than RIS-FG. These variations may explain the differences in severity of EPS between the 2 forms.

• Dosage forms
• 9-hydroxyrisperidone
• pharmacokinetics
• prolactin
• risperidone