Glucagon-like peptide-1 (GLP-1) is an incretin, a general term for gastrointestinal hormones that enhance insulin secretion in a glucose concentration-dependent manner. GLP-1 has been shown to improve blood glucose levels in patients with diabetes and promote extrapancreatic effects such as weight loss and lipid level improvements. The GLP-1 receptor agonists (GLP-1RAs) liraglutide and semaglutide have already been approved for weight loss treatment in addition to their use in treating type 2 diabetes in the United States and Europe, with specific conditions for obesity indications. In Japan, semaglutide has been approved as a treatment for obesity; however, it has not yet been marketed. Therefore, there have been reports on the unrestricted (off-label) use of GLP-1RAs for cosmetic and weight-loss purposes, which is considered problematic. As the use of GLP-1RAs is expected to increase in the future and is not limited to treating type 2 diabetes, this study investigated the use of GLP-1RAs and confirmed their safety in cell cultures exposed to GLP-1RAs. The culture of gastrointestinal epithelial cells using the three components of GLP-1RAs (liraglutide, semaglutide, and dulaglutide), which are prescribed in large quantities, suggested that exposure to high doses for 24 h did not affect cell viability or total cell protein content compared to controls, suggesting that the drug has not injurious after short-term exposure to the gastrointestinal epithelium.

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The incidence of diabetes mellitus increases with age and is expected to increase in the aging population of Japan. Although numerous drugs, ranging from oral to injectable formulations, have been developed for the treatment of diabetes, first-line medication is unavailable. Japan Diabetes Society states that blood glucose control goals should be set individually based on several factors, such as age, disease duration, complications, and risk of hypoglycemia. Drug selection should be based on the pathophysiology of each patient, considering the action and side effects of each drug. However, elderly people with diabetes are more likely that younger patients to develop side effects such as severe hypoglycemia, and care must be taken in the selection of therapeutic agents. Among the oral agents of concern for hypoglycemia are sulfonylurea (SU) drugs. Therefore, regional differences in the quantity of SU drugs prescribed were analyzed in this study, with the aim of preventing hypoglycemia and other problems. In addition, the age range of patients using SU drugs was investigated. The results showed that SU was widely used in the Kinki regions, but less so in Kyushu, indicating regional differences. In addition, approximately 60% of the patients taking SU drugs were ≥ 70 years old. Therefore, the study results suggest that the regional and age differences in the number of SU drug prescriptions should be taken into consideration when providing guidance to prevent hypoglycemia.

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近年、てんかんの薬物治療にはいくつかの新規薬物が導入されており、従来の薬で満足する効果が得られない患者では、しばしば併用治療が実施されている。これらの患者において薬物血中濃度と効果及び有害反応について、患者の多彩な臨床背景を加味して検討した報告は少ない。そこで本研究では、実臨床の場で抗てんかん薬物治療を受けた患者の、発作の寛解および有害事象発現を各種抗てんかん薬の血中濃度と患者背景と共に解析した。 調査対象は奈良医療センターてんかんセンターで薬物治療を受けた患者で、必要なデータは後方視的に診療録から抽出された。対象薬はバルプロ酸（VPA）の他、10薬物であった。収集された734名のデータは、単剤療法群（以下、単剤群）および多剤併用療法群（以下、多剤群）間で薬物治療効果と有害事象の有無について、薬物血中濃度と各種臨床背景を変動因子として統計的に解析された。治療効果は、発作の完全消失（寛解）と非寛解で評価し、有害事象については外来診察時に23種の自覚症状の有無を調査した。 VPA、カルバマゼピン（CBZ）、レベチラセタム、ラモトリギンの治療効果を単剤群で評価すると、寛解と非寛解の患者間で薬物血中濃度は有意差を認めなかった。また、どの薬物も寛解患者の4～5割程度で血中濃度がガイドラインで提唱されている参考薬物濃度域より低かった。多剤群の非寛解患者のVPA、CBZ、クロナゼパムの平均血中濃度は寛解患者より有意に高かった。一方、有害事象の発現の有無は、単剤群でも多剤群でも血中濃度に関連していなかった。さらに、単剤および多剤群における有害事象のない非寛解患者で、薬物血中濃度が参考濃度域より低かった患者が約2割存在することも明らかとなった。 　結論として、てんかんの薬物治療では単剤少量から開始し臨床効果を参照しつつ漸増する重要性が確認された。また、有害事象の発現なく寛解効果が得られていない患者は一定数存在し、血中薬物濃度を参照して薬剤師が抗てんかん薬の増量を提案できる可能性が示唆された。

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Glucagon-like peptide-1 receptor agonists provide good glycemic control and weight loss in patients with type 2 diabetes mellitus. Because of its large molecular weight, it has low permeability in the gastrointestinal tract and is liable to enzymatic degradation in the stomach. As a result, only an injectable formulation was developed and launched into the market. In recent years, however, an oral formulation of a glucagon-like peptide-1 receptor agonist, semaglutide, was developed by utilizing absorption enhancers. Nevertheless, a strict patient adherence to medication and proper drug management is required owing to a lower absorption with food, the stability and hygroscopicity of the oral formulation. To our knowledge, there are few case reports on the effects of differences in medication and drug management on therapeutic efficacy of the oral formulation of semaglutide. In this report, we present two patients who lost clinical efficacy of the drug due to different mechanisms of medication and drug management after switching from the injectable formulation to oral formulation of the drug. The patient with reliable medication and drug management maintained blood glucose levels similar to those noted treatment with the injectable formulation and lost weight. In contrast, in the poor medication and drug management patient, blood glucose levels and body weight deteriorated to those at the beginning of diabetes treatment; this was noted after 8 months of therapy with the oral formulation. Therefore, oral formulations requiring strict medication and drug management should thoroughly be monitored by pharmacists. In addition, it was also considered necessary to select an injectable drug not solely based on the method of management but also on factors such as the convenience of weekly management to ensure treatment.

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今日、柔軟仕上げ剤の利用が生活に定着する一方で、2008年以降柔軟仕上げ剤のマイクロカプセル製法による被害が報告されるようになった。本研究では、柔軟仕上げ剤など香りつき製品による被害の状況と体調の変化などについてwebアンケートを行い、結果を踏まえ環境衛生の観点から香害に対する薬剤師の役割を考察した。インターネット調査会社に登録している日本人男女を対象とし、有効回答は348人(有効回答率：94.6%)であった。香りつき製品による体調不良が「ある」と回答した人は21.8%であり、その具体的な症状では「吐き気」、「頭痛」、「くしゃみ・鼻水」が挙げられた。症状の原因と思われる製品として、「柔軟仕上げ剤」が44.7％と最も高かった。被害後は「人混みを避けるようになった」が26.3%であった。香りつき製品による被害をなくすための対策として「香りつき製品の使用についてルールを決める」が挙げられた。しかし、香りつき製品による健康被害や「香害」という言葉が社会に周知されていないため症状への理解を得られず、個人の嗜好の問題と誤解されることが危惧された。こうした状況に対し、薬剤師には環境衛生の観点から相談に応じること、企業や関連団体と連携し地域住民に対し香りのマナーや適正な使用、香害について啓蒙普及していく必要性が示唆された。

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