title: Effect of high-fat meal intake on the pharmacokinetic profile of ivermectin in Japanese patients with scabies.
abstract: Ivermectin (IVM) is used as an anthelmintic agent in many countries. To evaluate the effect of high-fat (HF) meal intake on the pharmacokinetics of IVM, a clinical trial was conducted in Japanese patients with scabies. The patients were administrated Stromectol(®) tablets in the fasted state, and after 1 week they were also administrated it after a HF meal (fed state). After the administration, IVM concentrations in plasma and the stratum corneum were determined. The geometric mean of fed/fasted ratio of area under IVM concentration-time curve (AUC) in plasma was 1.25 (90% confidence interval, 1.09-1.43), suggesting the tendency to increased absorption after a HF meal. The fed/fasted ratio of the maximum IVM concentration in the stratum corneum was well correlated with that in plasma. In addition, no serious adverse events were observed during the trial, while a mild increase of aspartate aminotransferase and alanine aminotransferase activity in plasma was observed under the fed state in two patients. The mean AUC of IVM in plasma of those two patients were approximately threefold higher than that of the other patients at that time. On the other hand, the treatment success rate was 76.9% at 7 days after the second administration, which was comparable with the expected level. The present study not only demonstrates that HF meal intake increases the IVM concentration in plasma and the stratum corneum in Japanese patients with scabies, but also suggests the possibility that HF meals increase the risk of hepatic dysfunction by the increased exposure of IVM.
authors.affiliation: Department of Biopharmaceutics, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Miyajima
authors.affiliation: Department of Biopharmaceutics, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Hirota
authors.affiliation: Department of Medical Safety, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda, Japan.
authors.forename: Akihito
authors.initials: A
authors.lastname: Sugioka
authors.affiliation: Department of Dermatology, Ina Central Hospital, Ina, Japan.
authors.forename: Masao
authors.initials: M
authors.lastname: Fukuzawa
authors.affiliation: Department of Dermatology, Ebara Hospital, Tokyo, Japan.
authors.forename: Mari
authors.initials: M
authors.lastname: Sekine
authors.affiliation: Department of Biopharmaceutics, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Yamamoto
authors.affiliation: Department of Medical Safety, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Yoshimasu
authors.affiliation: Department of Biopharmaceutics, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Kigure
authors.affiliation: Department of Biopharmaceutics, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda, Japan.
authors.forename: Taichi
authors.initials: T
authors.lastname: Anata
authors.affiliation: Department of Medical Safety, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Noguchi
authors.affiliation: Department of Medical Safety, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda, Japan.
authors.forename: Keita
authors.initials: K
authors.lastname: Akagi
authors.affiliation: Department of Medical Safety, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda, Japan.
authors.forename: Masayo
authors.initials: M
authors.lastname: Komoda
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000369:Aged, 80 and over; D000977:Antiparasitic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D059305:Diet, High-Fat; D004817:Epidermis / Q000378:metabolism; D005215:Fasting; D005260:Female; D006801:Humans; D007559:Ivermectin / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D007564:Japan; D008297:Male; D012532:Scabies / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D000977:Antiparasitic Agents; D007559:Ivermectin
keywords: high-fat meal; ivermectin; patients; pharmacokinetics; scabies