Pharmacokinetic Evaluation of Risperidone and Its Active Metabolite When Risperidone Oral Solution Is Mixed with Black Tea in Rats

Background/Objectives: Risperidone oral solution (RIS-OS) is an easy-to-administer treatment for schizophrenia designed to improve medication adherence and rapid onset of effect. Mixing RIS-OS with beverages such as black tea is prohibited due to reduced RIS concentrations observed in vitro, despite the absence of pharmacokinetic data. In this study, we evaluated the pharmacokinetics of RIS and its active metabolite 9-OH-RIS in rats following oral administration with black tea. Methods: Male Wistar rats received RIS-OS intravenously or orally as a water or Dimbula black tea mixture; serial tail-vein blood samples were collected as dried blood spots, RIS and 9-OH-RIS were quantified using HPLC/ESI-MS/MS, and pharmacokinetic parameters were calculated and compared using Welch’s t-test. Results: Compared with the water mixture, the black tea mixture significantly reduced RIS Cmax, while Tmax and AUC remained unchanged. Furthermore, AUMC and MRT were significantly higher. The results were similar for 9-OH-RIS. Despite reduced RIS content in vitro, no difference in absolute bioavailability was observed in vivo. Although only one black tea variety was tested, evaluating additional varieties may help identify the components responsible for reducing RIS content. Conclusions: Mixing RIS-OS with black tea may delay absorption without reducing overall exposure, providing evidence that may contribute to safer guidance regarding beverage coadministration.