# Preliminary Pharmacokinetics and Appetite Stimulant Efficacy of Oral Mirtazapine in Guinea Pigs (Cavia porcellus)

## TL;DR

This study explores the use of mirtazapine as an appetite stimulant in guinea pigs, finding it effective when administered every 8 hours.

## Contribution

The study establishes the dosing frequency for mirtazapine to stimulate appetite in guinea pigs.

## Key findings

- Mirtazapine increases feed intake in guinea pigs when administered every 8 hours.
- Peak plasma levels of mirtazapine occur within 30 minutes of administration.
- No significant weight gain differences were observed despite increased feed intake.

## Abstract

Guinea pigs are cecal fermenters requiring frequent and consistent feed intake to ensure normal gut motility. Transport, age-related disease, diet changes, and other sources of chronic stress can reduce their appetite, leading to gastrointestinal stasis which can be life threatening. Mirtazapine, a tetracyclic antidepressant, is used in dogs and cats to treat nausea and inappetence and has been shown to increase feed intake in cats. It has anecdotally been used as an appetite stimulant in guinea pigs, but a therapeutic dose of mirtazapine has not been established. Our work aims to look at the blood levels and physiologic effects of orally administered mirtazapine in guinea pigs.

Guinea pigs used in research may experience inappetence or decreased intestinal motility, which can significantly compromise their welfare. This study evaluates the use of mirtazapine on appetite and intestinal motility in guinea pigs. An initial pharmacokinetics and efficacy study was performed using healthy male guinea pigs administered mirtazapine at 1.88, 3.75, or 7.5 mg orally once daily for four days (n = 6), in a crossover design where all animals received all doses. Body, feed, and fecal weights were taken daily for 4 days. There were no significant differences in weight gains, feed intake, or fecal output as compared to guinea pigs given saline only (n = 3). Blood was collected under anesthesia at 0, 0.5, 1, 2, 8, 12, and 24 h post-administration. Pharmacokinetic analysis completed after the first dose showed peak plasma levels at 30 min, then falling below the limit of detection between 8 h and 12 h at all doses. Based on the pharmacokinetic profile, a follow-up study was performed in another set of healthy male guinea pigs with every 8 h dosing at 1.88 mg orally for 5 days (n = 6). There was a significant increase in feed intake during mirtazapine administration as compared to baseline intake, but no significant difference in weight gains. This study shows that mirtazapine can be used as an appetite stimulant in guinea pigs but must be dosed at least every eight hours to be effective.