Oral dosing of rodents using a palatable tablet

Abstract

Rationale: Delivering orally bioavailable drugs to rodents is an important component to investigating that route of administration in novel treatments for humans. However, the traditional method of oral gavage requires training, is stressful, and can induce oesophageal damage in rodents.

Objectives: To demonstrate a novel administrative technique-palatable gelatine tablets-as a stress-free route of oral delivery.

Methods: Twenty-four male Lister hooded rats were sacrificed for brain tissue analysis at varying time-points after jelly administration of 30 mg/kg of the wake-promoting drug modafinil. A second group of 22 female rats were tested on locomotor activity after 30 mg/kg modafinil, or after vehicle jellies, with the locomotor data compared to the brain tissue concentrations at the corresponding times.

Results: Modafinil was present in the brain tissue at all time-points, reducing in concentration over time. The pattern of brain tissue modafinil concentration is comparable to previously reported results following oral gavage. Modafinil-treated rats were more active than control rats, with greater activity during the later time-periods-similar to that previously reported following intraperitoneal injection of 40 mg/kg modafinil.

Conclusions: Palatable jelly tablets are an effective route of administration of thermally stable orally bioavailable compounds, eliminating the stress/discomfort and health risk of oral gavage and presenting as an alternative to previously reported palatable routes of administration where high protein and fat levels may adversely affect appetite for food reward, and uptake rate in the gastrointestinal tract.

Keywords: Locomotor activity; Modafinil; Oral administration; Pharmacokinetics.

Fig. 1

Locomotor activity: mean ± SEM number of infrared beams crossed after oral administration of either 30 mg/kg modafinil or vehicle jellies during time-periods from 15 to 160 min after administration. The wake-promoting effects of modafinil became obvious after the first time-period (“ns” denotes the single time-period where there was no significant difference between the groups), following a greater reduction in exploratory behaviour in the control group. Pharmacokinetic profile: mean ± SEM ng/g modafinil in brain tissue collected at specific time-points (within the first 5 mins of the 15 mins LMA time-periods) after oral administration of 30 mg/kg modafinil. Concentration reduced over time, although high variability at the 30-min time-point (within the 30–45-min time-period) may mask a true peak at the 60 min time-point (within the 60–75 min time-period)