Effect of fluvoxamine on the pharmacokinetics of paracetamol in mice

Introduction: Paracetamol is one of the most widely used analgesic and antipyretic drugs in the world. Fluvoxamine is a SSRI drug used in the treatment of depression. Fluvoxamine and paracetamol can be used simultaneously in treatment. In the combined use of drugs, drug-drug interactions may occur at the point of absorption, distribution, metabolism and excretion. The aim of this study was to determine the effect of low and high dose fluvoxamine administration on the pharmacokinetics of paracetamol in mice. Materials and Methods: In this study, 96 male Swiss Albino mice were used. Mice were divided into three groups with equal numbers (n=30). Paracetamol (700 mg/kg) was administered to the first group, paracetamol+low-dose (30 mg/kg) fluvoxamine to the second group, and paracetamol+high-dose (150 mg/kg) fluvoxamine to the third group. Plasma concentrations of paracetamol were assayed using HPLC and pharmacokinetic parameters were calculated by noncompartmental analysis. Results: After a single administration of paracetamol, t1/2ʎz, EAA and Cdoruk were 2.99 h, 880.72 h*μg/mL, and 486.74 μg/mL, respectively. Low and high dose fluvoxamine administration resulted in an increase in EAA 32% and 61%, and Cdoruk 15% and 27% of paracetamol, respectively. Conclusions: As a result, low and high dose fluvoxamine administration increased the plasma concentration of paracetamol in mice. This increase in the concentration of paracetamol, the effect of which is dose dependent, may lead to an increase in the therapeutic effect. However, further research is needed to determine the safety and mechanism of interaction following the concomitant use of paracetamol and fluvoxamine. Keywords: Pharmacokinetics, fluvoxamine, paracetamol