Pharmacokinetics and brain penetration of carbapenems in mice

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• 作者：Kazuaki Matsumoto^a ; ^{matsumoto-kz@pha.keio.ac.jp" class="auth_mail" title="E-mail the corresponding author} ; Yuji Kurihara^a ; ^b ; Yuko Kuroda^a ; Seiji Hori^c ; Junko Kizu^a
• 关键词：Carbapenems ; Pharmacokinetics ; Brain penetration
• 刊名：Journal of Infection and Chemotherapy
• 出版年：2016
• 出版时间：May 2016
• 年：2016
• 卷：22
• 期：5
• 页码：346-349
• 全文大小：336 K

文摘

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 CL_total/F, 1.41–2.03 h⁻¹ for K_e, 0.34–0.51 h for T_1/2, 0.66–0.95 L/kg for V_ss/F, 0.49–0.73 h for MRT, 83.46–110.58 μg/mL for C_{max, plasma}, and 0.28–0.83 μg/g for C_{max, brain tissue}. The AUC_0−∞ 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 AUC_{0−∞, brain tissue}/fAUC_{0−∞, 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.