新しいin vivo imaging systemとGFAP-Luc マウスを用いて、薬物動態を解析した。局所投与と全身 (静脈) 投与のそれぞれの単独投与群と局所と全身投与の併用群で薬物動態を観察比較した。そこで得られたシグナルのピークは、全身投与後よりも局所注入 (鼓室内投与) で早くみとめられた。局所投与のみ (TT-left) 群と比較して全身投与 (静脈注射) と局所投与併用 (CT-left) 群でtotal photon counts ならびにAUCは有意に増加していた。すなわち、内耳に取り込まれた総量は併用群で最も多く、次いで局所投与のみ群、静脈投与群の順であった。
We used a new in vivo imaging system to compare the pharmacokinetics of combined therapy (CT), with intravenous (IV) or transtympanic (TT) injection alone in both ears of transgenic GFAP-Luc mice. Biological half-life, total photon counts and the area under the curve (AUC) value significantly increased after CT. However, adding IV to TT injection cannot strengthen
the peak photon of the drug in the inner ear. In addition, the volume of total photon count and AUC value of CT-left ear are larger than the combined volume of TT-left ear and IV-left ear, suggesting a synergistic effect, and those of CT-right ear are almost equal to the summation of those of IV-right group and TT-right group, suggesting no amplifying effect on the risk of systemic side effect. This study showed that CT could deliver more drugs into the inner ear, and brought a longer therapeutic window, and were more effective than intravenous or transtympanic injection alone in the pharmacokinetics.

研究種目 : 基盤研究 (C) (一般)
研究期間 : 2015～2018
課題番号 : 15K10762
研究分野 : 耳鼻咽喉科