著者

Kazuaki Matsumoto Masaru Samura Sho Tashiro Shino Shishido Reika Saiki Wataru Takemura Kana Misawa Xiaoxi Liu Yuki Enoki Kazuaki Taguchi

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.824-833, 2022-07-01 (Released:2022-07-01)

参考文献数

69

被引用文献数

6

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The target therapeutic ranges of vancomycin, teicoplanin, and arbekacin have been determined, and therapeutic drug monitoring (TDM) is performed in clinical practice. However, TDM is not obligatory for daptomycin, linezolid, or tedizolid. In this study, we examined whether TDM will be necessary for these 3 drugs in the future. There was no significant difference in therapeutic effects on acute bacterial skin and skin structure infection between linezolid and tedizolid by meta-analysis. Concerning the therapeutic effects on pneumonia, the rate of effectiveness after treatment with tedizolid was significantly lower than with linezolid. With respect to safety, the incidences of gastrointestinal adverse events and blood/lymphatic system disorders related to tedizolid were significantly lower than those related to linezolid. Linezolid exhibits potent therapeutic effects on pneumonia, but the appearance of adverse reactions is indicated as a problem. There was a dose-dependent decrease in the platelet count, and the target trough concentration (Ctrough) was estimated to be 4–6 or 2–7 µg/mL in accordance with the patient’s condition. The efficacy of linezolid may be obtained while minimizing the appearance of adverse reactions by performing TDM. The target therapeutic range of tedizolid cannot be achieved in immunocompromised or severe patients. Therefore, we concluded that TDM was unnecessary, considering step-down therapy with oral drugs, use in non-severe patients, and high-level safety. Concerning daptomycin, high-dose administration is necessary to achieve an area under the curve (AUC) of ≥666 as an index of efficacy. To secure its safety, Ctrough (<20 µg/mL) monitoring is important. Therefore, TDM is necessary.

著者

Go Ando Kazuaki Taguchi Yuki Enoki Yuta Yokoyama Junko Kizu Kazuaki Matsumoto

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.42, no.11, pp.1799-1804, 2019-11-01 (Released:2019-11-01)

参考文献数

20

被引用文献数

22

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Investigation of the occurrence time of adverse drug reactions helps to prevent the development and aggravation of adverse reactions, but the expression time of ganciclovir-induced adverse events has not been elucidated. In this study, using databases of spontaneous adverse event reports, the Japanese Adverse Drug Event Report database (JADER) and the U.S. Food and Drug Administration (FDA)’s Adverse Event Reporting System (FAERS), the incidence of adverse reactions due to ganciclovir and their expression time were analyzed. As a result of calculation of the reporting odds ratio (ROR) and 95% confidence interval for individual main adverse reactions of ganciclovir (cytopenia, leukopenia, thrombocytopenia, liver damage, and acute renal failure), a signal was detected for all adverse reactions in both databases, except for liver damage in JADER. Furthermore, the Weibull distribution was performed for the analysis of onset time of each ganciclovir-induced adverse event. The results of Weibull parameter α and β values of each adverse event in both JADER and FAERS suggested that most adverse events occurred within 30 d and classified into the early failure type, except that thrombocytopenia and acute renal failure in JADER classified into the random failure type. Based on these findings, it concluded that the paying attention to signs of each ganciclovir-induced adverse event is required from the early phase after ganciclovir administration. However, in FAERS, development after a long-term course also accounted for 11%, suggesting that long-term periodic monitoring of adverse reactions would be also required.

著者

Takashi Hasegawa Kenji Tsukigawa Kindness Commey Mina Sakuragi Shuhei Imoto Kazuaki Taguchi Koji Nishi Masaki Otagiri Keishi Yamasaki

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.72, no.1, pp.21-27, 2024-01-01 (Released:2024-01-01)

参考文献数

28

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Pirarubicin (THP) shows more rapid intracellular uptake, more effective antitumor activity, and less cardiac toxicity, compared to doxorubicin. However, THP is distributed to both tumor and normal tissues indiscriminately. This study aimed to develop a nanosuspension to deliver THP to tumor tissues more efficiently. Fatty-acid-modified THPs (FA-THPs; octanoic acid, dodecanoic acid, palmitic acid-THPs) were synthesized to increase the hydrophobicity of THP. Nanosuspensions of these FA-THPs were then prepared using an antisolvent precipitation technique. Among the FA-THPs, the most efficiently drug-loaded nanosuspension was obtained from palmitic acid-THP (pal-THP) using an aqueous antisolvent containing bovine serum albumin as a stabilizer. The pal-THP nanoparticles in the nanosuspension were confirmed to be of optimal size (100–125 nm) for delivery to tumor tissues using dynamic light scattering and transmission electron microscopy. The pal-THP nanosuspension showed cytotoxicity in colon 26 cells. The nanosuspension was shown to disintegrate in the presence of surfactants such as lecithin, liberating pal-THP, which was converted to free THP in acidic media. It is therefore proposed that pal-THP nanoparticles that reach tumor cells after intravenous administration would exert antitumor effect by liberating pal-THP (i.e., disintegration of nanoparticles by the interaction with cell membrane), followed by the release of free THP in the acidic milieu of tumor cells. These findings indicate that FA-THP nanosuspensions, particularly pal-THP nanosuspension, hold promise as a candidate for cancer treatment. However, further in vivo studies are necessary.