title: Pharmacokinetics and brain penetration of carbapenems in mice.
abstract: An adverse effect associated with the administration of carbapenems is central nervous system (CNS) toxicity, with higher brain concentrations of carbapenems being linked to an increased risk of seizures. However, the pharmacokinetics and brain penetration of carbapenems have not yet been examined. Thus, the aim of this in vivo investigation was to determine the pharmacokinetics and brain penetration of carbapenems in mice. Blood samples and brain tissue samples were obtained 10, 20, 30, 60, and 120 min after the subcutaneous administration of carbapenems (91 mg/kg). We obtained the following values for the pharmacokinetic parameters of carbapenems in mice: 1.20-1.71 L/h/kg for CLtotal/F, 1.41-2.03 h(-1) for Ke, 0.34-0.51 h for T1/2, 0.66-0.95 L/kg for Vss/F, 0.49-0.73 h for MRT, 83.46-110.58 μg/mL for Cmax, plasma, and 0.28-0.83 μg/g for Cmax, brain tissue. The AUC0-∞ of the carbapenems tested in plasma were in the following order: doripenem > meropenem > biapenem > imipenem, and in brain tissue were: imipenem > doripenem > meropenem > biapenem. The degrees of brain tissue penetration, defined as the AUC0-∞, brain tissue/fAUC0-∞, plasma ratio, were 0.016 for imipenem, 0.004 for meropenem, 0.002 for biapenem, and 0.008 for doripenem. The results of the present study demonstrated that, of the carbapenems examined, imipenem penetrated brain tissue to the greatest extent.
authors.affiliation: Division of Practical Pharmacy, Keio University Faculty of Pharmacy, 1-5-30 Shibakoen, Minato-ku, Tokyo 105-8512, Japan. Electronic address: matsumoto-kz@pha.keio.ac.jp.
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Matsumoto
authors.affiliation: Division of Practical Pharmacy, Keio University Faculty of Pharmacy, 1-5-30 Shibakoen, Minato-ku, Tokyo 105-8512, Japan; Molecular Medical Bioscience Laboratory, Yokohama City University Graduate School of Medical Life Science, 1-7-29 Suehiro-cho, Turumi-ku, Yokoyama 230-0045, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kurihara
authors.affiliation: Division of Practical Pharmacy, Keio University Faculty of Pharmacy, 1-5-30 Shibakoen, Minato-ku, Tokyo 105-8512, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Kuroda
authors.affiliation: Department of Infectious Diseases and Infection Control, Jikei University School of Medicine, 3-25-8 Nishi-Shinbashi, Minato-ku, Tokyo 105-8461, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Hori
authors.affiliation: Division of Practical Pharmacy, Keio University Faculty of Pharmacy, 1-5-30 Shibakoen, Minato-ku, Tokyo 105-8512, Japan.
authors.forename: Junko
authors.initials: J
authors.lastname: Kizu
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics*; D001921:Brain / Q000378:metabolism*; D001923:Brain Chemistry / Q000187:drug effects*; D015780:Carbapenems / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics*; D007279:Injections, Subcutaneous; D051379:Mice
chemical_list: D000900:Anti-Bacterial Agents; D015780:Carbapenems
keywords: Brain penetration; Carbapenems; Pharmacokinetics