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All Journal IDJP (Indonesian Journal of Pharmaceutics)
Yashima, Hideaki
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Risk of Falls with Benzodiazepine Receptor Agonists in Combination with Novel hypnotics. Higuchi, Yuya; Ishikawa, Yuya; Araki, Takuya; Ohshima, Yukina; Yashima, Hideaki; Yamamoto, Koujirou
Indonesian Journal of Pharmaceutics Vol 5, Issue 2, May - August 2023
Publisher : Universitas Padjadjaran (Unpad)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.24198/idjp.v5i2.52528

Abstract

Several risk factors for falls during hospitalization have been reported, of which hypnotics have a major influence. Insomnia is often intractable, and many cases are treated with two or more hypnotics; however, there is concern about the increased risk of falls due to the use of multiple hypnotics. Therefore, we aimed to clarify the effects of combining conventional and new hypnotics on the risk of falls. The impact of the concomitant use of hypnotics on the occurrence of fall events was evaluated retrospectively in patients 20 years of age and older received acute care medicine in an university hospital between January 2013 and August 2022. The survey items included age, sex, drug prescription status, whether a fall accident had occurred, and its circumstances. Of the 47,236 eligible patients, 976 experienced a fall accident during hospitalization (fall rate, 2.07%). Logistic regression analysis of the patient population not taking benzodiazepine receptor agonists showed that age (odds ratio [OR], 1.04), sex (OR, 0.84), and ramelteon use (OR, 3.06) independently contributed to falls. In contrast, in the patient population taking benzodiazepine receptor agonists, logistic regression analysis showed that only age (odds ratio [OR]: 1.03) and sex (OR: 0.76) independently contributed to falls. This suggests that ramelteon, suvorexant, and lemborexant, in combination with benzodiazepines, may not increase the risk of falls. Hypnotics with novel mechanisms of action may not increase the risk of fall when combined with benzodiazepine receptor agonists.
Impact of Sample Preparation Methods on LC-MS/MS Analysis of Molecular Targeted Drugs Tanaka, Yusuke; Araki, Takuya; Yashima, Hideaki; Yamamoto, Koujirou
Indonesian Journal of Pharmaceutics Vol 7, Issue 1, Jan - April 2025
Publisher : Universitas Padjadjaran (Unpad)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.24198/idjp.v7i1.60748

Abstract

The therapeutic efficacy of molecular targeted drugs (MTD)s and the risk of certain adverse drug effects are closely related to their blood concentrations, highlighting the importance of optimizing dosage based on therapeutic drug monitoring. In this study, we compared four pretreatment methods for the analysis of 15 MTDs by LC-MS/MS: protein precipitation (PPT), solid-phase extraction (SPE) using a reversed-phase (RP) column, SPE using a mixed-mode cation-exchange RP column, and supported liquid extraction (SLE), and evaluated their effects on recovery rates and matrix effects. While PPT showed high recovery rates (>80%) for 8 out of 15 compounds, certain highly polar MTDs exhibited significant peak intensity decreases with repeated analyses, indicating potential issues with ion suppression due to impurities. SPE using a reversed-phase column (HLB) resulted in low recovery rates for 12 out of 15 compounds. In contrast, SPE using an MCX column yielded high recovery rates (>80%) for 14 out of 15 compounds but exhibited substantial matrix effects for 9 out of 15 compounds (matrix factors >2). Addressing these matrix effects required sample dilution, and achieving higher sensitivity would necessitate extensive method adjustments tailored to each compound. SLE demonstrated the most favorable results, with the largest number of compounds showing acceptable recovery rates and minimal matrix effects. In conclusion, these findings, based on standard protocols from product manuals, suggest that while method optimization could improve performance for specific compounds, SLE appears to be the most suitable first-choice pretreatment method for the LC-MS/MS analysis of MTDs due to its balance of recovery and matrix effect control.
Co-Authors Araki, Takuya Higuchi, Yuya Ishikawa, Yuya Ohshima, Yukina Tanaka, Yusuke Yamamoto, Koujirou