title: Oral toxicity of Miglyol 812(®) in the Göttingen(®) minipig.
abstract: Miglyol 812(®), 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 Göttingen(®) 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(®) 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(®) 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.
authors.affiliation: Preclinical Development, Galderma R&D, Biot, France. Electronic address: gwenaelle.lebars@galderma.com.
authors.forename: G
authors.initials: G
authors.lastname: Le Bars
authors.affiliation: Preclinical Development, Galderma R&D, Biot, France.
authors.forename: S
authors.initials: S
authors.lastname: Dion
authors.affiliation: Preclinical Development, Galderma R&D, Biot, France.
authors.forename: B
authors.initials: B
authors.lastname: Gauthier
authors.affiliation: Preclinical Development, Galderma R&D, Biot, France.
authors.forename: S
authors.initials: S
authors.lastname: Mhedhbi
authors.affiliation: KALEIDIS, Consultancy in Histopathology, St Louis, France.
authors.forename: G
authors.initials: G
authors.lastname: Pohlmeyer-Esch
authors.affiliation: Preclinical Development, Galderma R&D, Biot, France.
authors.forename: P
authors.initials: P
authors.lastname: Comby
authors.affiliation: Preclinical Development, Galderma R&D, Biot, France.
authors.forename: N
authors.initials: N
authors.lastname: Vivan
authors.affiliation: Preclinical Development, Galderma R&D, Biot, France.
authors.forename: B
authors.initials: B
authors.lastname: Ruty
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D004334:Drug Administration Schedule; D004435:Eating / Q000187:drug effects; D005260:Female; D008168:Lung / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D014677:Pharmaceutical Vehicles / Q000008:administration & dosage / Q000633:toxicity*; D011015:Pneumonia, Aspiration / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D012119:Respiration; D018570:Risk Assessment; D013552:Swine; D013556:Swine, Miniature; D013997:Time Factors; D014280:Triglycerides / Q000008:administration & dosage / Q000633:toxicity*
chemical_list: D014677:Pharmaceutical Vehicles; D014280:Triglycerides; C022834:miglyol 812
keywords: Medium-chain triglycerides; Miglyol 812(®); Minipig; Oral; Toxicity; Vehicle