著者

Toshinori Hirai Hidefumi Kasai Masahiro Takahashi Satomi Uchida Naoko Akai Kazuhiko Hanada Toshimasa Itoh Takuya Iwamoto

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.45, no.7, pp.948-954, 2022-07-01 (Released:2022-07-01)

参考文献数

35

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Some population pharmacokinetic models for amiodarone (AMD) did not incorporate N-desethylamiodarone (DEA) concentration. Glucocorticoids activate CYP3A4 activity, metabolizing AMD. In contrast, CYP3A4 activity may decrease under inflammation conditions. However, direct evidence for the role of glucocorticoid or inflammation on the pharmacokinetics of AMD and DEA is lacking. The pilot study aimed to address this gap using a population pharmacokinetic analysis of AMD and DEA. A retrospective cohort observational study in adult patients who underwent AMD treatment with trough concentration measurement was conducted at Tokyo Women’s Medical University, Medical Center East from June 2015 to March 2019. Both structural models of AMD and DEA applied 1-compartment models, which included significant covariates using a stepwise forward selection and backward elimination method. The eligible 81 patients (C-reactive protein level: 0.26 [interquartile range; 0.09–1.92] mg/dL) had a total of 408 trough concentrations for both AMD and DEA. The median trough concentrations were 0.49 [0.31–0.81] µg/mL for AMD and 0.43 [0.28–0.71] µg/mL for DEA during a median follow-up period of 446 [147–1059] d. Three patients received low-dose oral glucocorticoid. The final model identified that AMD clearance was 7.9 L/h, and the apparent DEA clearance was 10.3 L/h. Co-administered glucocorticoids lowered apparent DEA clearance by 35%. These results indicate that co-administered glucocorticoids may increase DEA concentrations in patients without severe inflammation.

著者

Kazutaka Aonuma Tsuyoshi Shiga Hirotsugu Atarashi Kosuke Doki Hirotoshi Echizen Nobuhisa Hagiwara Junichi Hasegawa Hideharu Hayashi Kenzo Hirao Fukiko Ichida Takanori Ikeda Yorinobu Maeda Naoki Matsumoto Toshiyuki Sakaeda Wataru Shimizu Mitsuru Sugawara Kyoichi Totsuka Yoshimasa Tsuchishita Kazuyuki Ueno Eiichi Watanabe Masayuki Hashiguchi Sumio Hirata Hidefumi Kasai Yoshiaki Matsumoto Akihiko Nogami Yukio Sekiguchi Tokuko Shinohara Atsushi Sugiyama Naokata Sumitomo Atsushi Suzuki Naohiko Takahashi Eiji Yukawa Masato Homma Minoru Horie Hiroshi Inoue Hiroshi Ito Takanori Miura Tohru Ohe Kimikazu Shinozaki Kazuhiko Tanaka on behalf of the Japanese Circulation Society and the Japanese Society of Therapeutic Drug Monitoring Joint Working Group

出版者

The Japanese Circulation Society

雑誌

Circulation Journal (ISSN:13469843)

巻号頁・発行日

vol.81, no.4, pp.581-612, 2017-03-24 (Released:2017-03-24)

参考文献数

185

被引用文献数

33