Oral toxicity of Miglyol 812 registered in the Gottingen registered minipig

• Published in: Regulatory toxicology and pharmacology 2015-12, Vol.73 (3), p.930-937
• Main Authors: Le Bars, G, Dion, S, Gauthier, B, Mhedhbi, S, Pohlmeyer-Esch, G, Comby, P, Vivan, N, Ruty, B
• Format: Article
• Language: English
• ISSN: 0273-2300
• DOI: 10.1016/j.yrtph.2015.09.022

Miglyol 812 registered , a mixture of medium-chain triglycerides, has been identified as an oral vehicle that could improve the solubility and possibly the bioavailability of orally administered drugs during the non-clinical safety assessment. The toxicity of Miglyol was assessed in Gottingen registered minipigs upon daily oral administration (gavage) for six weeks, at dosing-volumes of 0.5 and 2 mL/kg/day, compared to controls receiving 0.5% CarboxyMethylCellulose/0.1% Tween registered 80 in water at 2 mL/kg/day. The control vehicle did not induce any findings. Miglyol at 0.5 and 2 mL/kg/day induced transient tremors, abnormal color of feces and increase in triglycerides. Miglyol at 2 ml/kg/day also induced reduced motor activity, decreased food intake, respiratory signs (2/6 animals) and increased total and LDL-cholesterol. At necropsy, the lung of 3/6 animals treated at 2 mL/kg/day presented abnormal color and/or irregular surface correlated with a chronic bronchiolo-alveolar inflammation. This finding is probably due to aspiration pneumonia in relation to the administration method and the high viscosity of Miglyol. Overall, the oral administration of pure Miglyol 812 registered for six weeks up to 2 mL/kg was less tolerated than that of the control vehicle. Miglyol as vehicle for sub-chronic oral toxicity studies in minipigs should be used with a limited dosing-volume.