title: The pharmacokinetics of mianserin suppositories for rectal administration in dogs and healthy volunteers: a pilot study.
abstract: BACKGROUND
  We formulated mianserin suppositories for the treatment of delirium and evaluated their pharmacokinetics by measuring plasma drug concentrations in dogs and healthy human volunteers.
  
  
  METHODS
  Mianserin suppositories were prepared by a melting technique using Tetramide® tablets and Witepsol H-15 as the suppository base. Pharmacokinetics of this 30-mg mianserin preparation were evaluated in three beagle dogs and three healthy adult males, in line with ethics committee approval. Plasma mianserin levels were determined using gas chromatography-mass spectrometry.
  
  
  RESULTS
  In dogs, the maximum plasma mianserin concentration (Cmax) was 1.3 ± 0.4 ng/mL, the time to Cmax (tmax) was 5.5 ± 4.3 h, and the area under the plasma concentration-time curve from 0 to 24 h (AUC0-24) was 18.9 ± 1.9 h・ng/mL. In humans, the Cmax was 14.6 ± 6.3 ng/mL, the tmax was 8 h, and the AUC0-24 was 266 ± 103 h・ng/mL.
  
  
  CONCLUSIONS
  The current study characterized the pharmacokinetics of mianserin suppositories in dogs and humans. As compared to oral administration, the suppositories produced a lower Cmax and a delayed tmax, although AUC0-24 values were comparable. It will be necessary to identify an appropriate dose that produces an adequate plasma mianserin concentration for effective and safe clinical use.
  
  
  BACKGROUND
  UMIN000013853.
authors.affiliation: Pharmaceutical Department, Yokohama City University Medical Center, 4-57 Urafune, Minami-ku, Yokohama, 232-0024 Japan ; Division of Clinical Pharmacy, Department of Pharmacotherapeutics, Showa University School of Pharmacy, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8555 Japan.
authors.forename: Shuichi
authors.initials: S
authors.lastname: Nawata
authors.affiliation: Division of Clinical Pharmacy, Department of Pharmacotherapeutics, Showa University School of Pharmacy, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8555 Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Kohyama
authors.affiliation: Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University Karasuyama Hospital, 6-11-11 Kitakarasuyama, Setagaya-ku, Tokyo, 157-8577 Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Uchida
authors.affiliation: Division of Toxicology, Department of Pharmacology, Toxicology & Therapeutics, Showa University School of Pharmacy, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8555 Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Numazawa
authors.affiliation: Division of Clinical Pharmacy, Department of Pharmacotherapeutics, Showa University School of Pharmacy, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8555 Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Ohbayashi
authors.affiliation: Division of Clinical Pharmacy, Department of Pharmacotherapeutics, Showa University School of Pharmacy, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8555 Japan.
authors.forename: Yasuna
authors.initials: Y
authors.lastname: Kobayashi
authors.affiliation: Department of Clinical Pharmaceutics, Yokohama College of Pharmacy, 601 Matano-cho, Totsuka-ku, Yokohama, 245-0066 Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Iwata
authors.affiliation: Clinical Pharmacy Educational Center, Nihon Pharmaceutical University, 10281 Komuro, Ina-cho Kita-adachi-gun, Saitama, 362-0806 Japan.
authors.forename: Takanori
authors.initials: T
authors.lastname: Nakajima
authors.affiliation: Clinical Pharmacy Educational Center, Nihon Pharmaceutical University, 10281 Komuro, Ina-cho Kita-adachi-gun, Saitama, 362-0806 Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Saito
authors.affiliation: Clinical Pharmacy Educational Center, Nihon Pharmaceutical University, 10281 Komuro, Ina-cho Kita-adachi-gun, Saitama, 362-0806 Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Izuka
authors.affiliation: Division of Clinical Pharmacy, Department of Pharmacotherapeutics, Showa University School of Pharmacy, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8555 Japan.
authors.forename: Toshinori
authors.initials: T
authors.lastname: Yamamoto
keywords: Delirium; Mianserin; Pharmacokinetics; Suppository