title: Effect of high fat intake on the pharmacokinetic profile of ivermectin in rabbits.
abstract: Ivermectin (IVM) is used as an oral drug for treatment of scabies. It was reported that the area under the plasma concentration-time curve (AUC) of IVM was higher in healthy volunteers after a high-fat meal than in those who were fasting, but the mechanism has not been clarified yet. In fasted rabbits, the AUC after oral administration of IVM as a solution was higher than that of a suspension, indicating that the absorption of IVM depends on how much is dissolved in the gastrointestinal tract. On the other hand, the AUC was higher in rabbits pre-treated with a high-fat solution (HF; fat and cholesterol) than in those that had fasted, when IVM was administered orally not only in suspension but also in solution, and even when it was administered intravenously. In addition, the increase in total cholesterol level in the HF condition was correlated with the increase in IVM level. These results suggest that enhancement of solubility may not be the only reason for the increase of AUC in rabbits. It is also suggested that the increase of cholesterol concentration might change the distribution profile of IVM in plasma, and accordingly its concentration could be increased.
authors.affiliation: Department of Biopharmaceutics, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda-shi, Chiba 278-8510, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Miyajima
authors.affiliation: Department of Biopharmaceutics, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda-shi, Chiba 278-8510, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Yamamoto
authors.affiliation: Department of Biopharmaceutics, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda-shi, Chiba 278-8510, Japan. Electronic address: hirotas5@rs.noda.tus.ac.jp.
authors.forename: Takashi
authors.initials: T
authors.lastname: Hirota
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000977:Antiparasitic Agents / Q000008:administration & dosage / Q000097:blood* / Q000737:chemistry; D019540:Area Under Curve; D004041:Dietary Fats / Q000008:administration & dosage* / Q000494:pharmacology*; D065569:Gastrointestinal Absorption; D007275:Injections, Intravenous; D007559:Ivermectin / Q000008:administration & dosage / Q000097:blood* / Q000737:chemistry; D008297:Male; D011817:Rabbits; D012995:Solubility; D012996:Solutions; D013535:Suspensions
chemical_list: D000977:Antiparasitic Agents; D004041:Dietary Fats; D012996:Solutions; D013535:Suspensions; D007559:Ivermectin
keywords: High-fat meal; Ivermectin concentration; Lipoprotein; Rabbits; Total cholesterol