薬理と治療
Volume 48, Issue 8, 2020
Volumes & issues:
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扉・目次
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TOPIC 第19回CRCと臨床試験のあり方を考える会議 2019 in YOKOHAMA
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- <シンポジウム14>再生医療等製品の治験—基本を知って備えよう—
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ORIGINAL ARTICLES
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2 型糖尿病に対するダパグリフロジンの安全性および有効性の検討―長期使用に関する特定使用成績調査の最終報告(DAHLIA 試験)―
48巻8号(2020);View Description Hide DescriptionBackground A special drug use-results survey was begun in September 2014 to investigate the safety and efficacy of the SGLT2 inhibitor dapagliflozin(Forxiga® Tablets)during long-term post-marketing use. Here, we report the final results of that survey. Methods A special drug use-results survey was conducted in type 2 diabetes patients receiving dapagliflozin for the first time, with a maximum observation period of three years. The survey was conducted to explore the occurrence of adverse drug reactions(ADRs)designated as key investigation items and their risk factors, and to investigate factors that might affect safety and efficacy, etc., and the ADRs unexpected from the precautions for use and ADRs under actual drug use. Changes from baseline in HbA1c(NGSP), fasting blood glucose, random blood glucose, body weight, body mass index, and blood pressure were investigated to evaluate efficacy. Results The size of the safety population was 7581 patients, and that of the efficacy population was 7359 patients. ADRs were found in 981 patients(12.9%), with the most frequent being pollakiuria in 70 patients(0.9%)and pruritus genital in 51 patients(0.7%). Serious ADRs were seen in 135 patients(1.8%), with those occurring in five or more patients being cerebral infarction in 12 patients(0.2%), acute myocardial infarction in nine patients (0.1%), dehydration in seven patients(0.1%), angina pectoris in six patients (0.1%), and colon cancer in five patients(0.1%). The incidences of ADRs designated as priority survey items were 2.8% for genital/urinary tract infection-related ADRs, 0.4% for hypoglycaemia-related ADRs, 1.2% for polyuria/pollakiuria-related ADRs, 1.2% for fluid loss-related ADRs, 0.8% for cardiovascular /cerebrovascular disease-related ADRs, 0.1% for weight decreased -related ADRs, 1.0% for skin disorder-related ADRs, 0.8% for renal impairment-related ADRs, 0.7% for hepatic function disorder-related ADRs, 0.6% for ketone body increased-related ADRs, 0.3% for malignant tumor-related ADRs, and 0.1% for bone metabolism-related ADRs. Downward trends in HbA1c, fasting blood glucose, random blood glucose, body weight, body mass index, and blood pressure were found during the 36 months with administration of dapagliflozin. Conclusion No apparent issues related to the safety profile of dapagliflozin were observed, and no particular efficacy-related concerns were found, during long-term post-marketing use for three years. -
2 型糖尿病患者に対するアナグリプチン・メトホルミン配合錠の安全性および有効性の検討―一般使用成績調査 中間報告―
48巻8号(2020);View Description Hide DescriptionBackground and Objectives METOANA® LD/HD is a combination tablet containing 250 mg or 500 mg metformin hydrochloride and 100 mg anagliptin. A drug use results survey of METOANA® is currently underway. In this interim analysis, we examined the safety and efficacy after 24 weeks of treatment in real-world clinical settings, excluding cases currently under study. Methods Patients with type 2 diabetes who were newly treated with METOANA® were included in this study. Adverse events, efficacy endpoints and others were surveyed using a central registry system. Results The incidence of adverse drug reactions in safety analysis set(412 patients)was 4.37%(18 patients), including constipation(0.97%), acute myocardial infarction(0.49%), anaemia, hypoglycaemia, organising pneumonia, abdominal pain, abdominal pain upper, gastritis, nausea, diabetic nephropathy, renal impairment, oedema peripheral, blood triglycerides increased, and hepatic enzyme increased(0.24% each). Serious side effects included organising pneumonia in 1 patient(0.24%)and acute myocardial infarction in 2 patients(0.49%) occurred. The efficacy of this drug was maintained up to 24 weeks, and the mean change in HbA1c at the final evaluation was -0.39±1.04(SD)%. Conclusions No new safety or efficacy issues were observed during 24 weeks of use, suggesting that METOANA® LD╱HD is a useful treatment option for patients with type 2 diabetes. -
クロモジ熱水抽出物のインフルエンザウイルス感染抑制メカニズムの検討
48巻8号(2020);View Description Hide DescriptionBackground The branches of the Kuromoji(Lindera umbellata Thunb.)have long been used as a herbal medicine and in modern times as an ingredient for medicinal liquor. We have reported that a hot-water extract of branches of Kuromoji (Kuromoji extract)has a sustained suppressive effect on the growth of type-A influenza virus strain. In this study, we investigated the efficacy of Kuromoji extract against other type-A influenza virus strains and the point of action of its antiviral activity. Methods The inhibitory effect of Kuromoji extract on the cytopathic effect by swine-origin pandemic influenza virus strain and its oseltamivir-resistant variant was investigated. The most effective time of treatment with Kuromoji extract in viral infection was examined by quantifying viral RNA and viral protein expression in host cells. The effect on the viral adsorption process was examined by hemagglutination inhibition test. Results The anti-influenza virus activity of Kuromoji extract against human influenza A viruses including swine-origin influenza strains and its oseltamivir-resistant variant and was observed. Kuromoji extract was most effectively suppressed viral mRNA expression in host cells when added 0-30 min after the virus inoculation. In the presence of Kuromoji extract, inhibition of hemagglutination by the virus was observed. In comparison with the inactivating effect on virus particle, host cell︱mediated inhibitory effect on viral growth was exerted even at a lower concentration. Conclusions Kuromoji extract was suggested to suppress the process from adsorption to uncoating in influenza virus infection mainly by the action via host cells. We believe Kuromoji extract is one of the useful functional food materials that prevent influenza virus infection. -
健康中高年男女を対象としたリバスチグミン含有経皮吸収型製剤(HP—1040)の皮膚刺激性の評価
48巻8号(2020);View Description Hide DescriptionObjectives While rivastigmine-containing transdermal patches are effective for the treatment for Alzheimerʼs diseases, there have been known some cases who could not continue the treatment because of skin irritation at the local application site. HP-1040 has been developed as a generic of rivastigmine patch with the 3-times expanding area for topical application. HP-1040 is expected to reduce skin irritation at the local application site because a drug concentration per unit area of HP-1040 is 1/3 lower compared to the original drug. We conducted randomized, non-blinded clinical trial which aims to compare the skin irritation between HP-1040 and the original drug. Methods We conducted an open-label, multiple-dose study for 40 healthy middle-aged and elderly volunteers that each one sheet of HP-1040 and the original drug is to be put on the fixed and separated part of the body and skin assessment was conducted everyday. Results The skin irritation score of HP-1040, a primary endpoint, was significantly lower than that of the original drug. The incidence of erythema at the application site of HP-1040 was half that of the original drug, however similar incidences of pruritus were shown on the application sites of HP-1040 and the original drug. Conclusions HP-1040 was considered to be a formulation with reduced skin irritation than the original drug(. jRCTs031190145) -
中心静脈栄養用総合ビタミン製剤投与による,慢性腎臓病患者へのビタミンA およびC の負荷に関する検討―多施設共同前向き観察研究―
48巻8号(2020);View Description Hide DescriptionObjectives According to the guidelines in other countries, the recommended doses of vitamin A(VA)and vitamin C(VC)administered to patients with chronic kidney disease(CKD) during intravenous nutrition are less than those to general patients due to concerns of vitamin overload. In the present study, we examined whether total parenteral nutrition(TPN)management using multivitamin preparations for TPN cause an overload of VA and VC. Methods We conducted a multicenter prospective observational study and measured the serum levels of VA and VC in CKD patients receiving and not receiving TPN. Results Regardless of TPN administration, the serum levels of CKD patients receiving VA and VC were rarely elevated. Conclusions Our findings suggested that the risk of overload was low even if multivitamin preparation for TPN were administered to CKD patients on a daily basis for about 2 weeks. A more aggressive supplementation of VC should be considered in maintenance hemodialysis patients with poor VC intake from sources other than TPN. (UMIN Clinical Trials Registry ID:UMIN000028425) -
Effects of Fish Meat—derived Peptides on Fatigue
48巻8号(2020);View Description Hide DescriptionObjectives Basic-research studies have reported the anti-fatigue effects of peptides and proteins derived from fish meat. However, very few full-scale investigations using randomized control trials(RCT)have been carried out to elucidate these effects so far. In this context, we conducted an investigative research using RCT on the effects of fish meat-derived peptides on improvement in alleviation of fatigue. Methods We prepared tablets containing fish meat-derived peptides or placebo to administer to subjects in a“fish meat-derived peptides group”and a“placebo group”, respectively. Results The administration of fish meat -derived peptides caused no adverse events based on hematological values, and none of the patients required treatment at the study site. There were no significant differences observed in any hematological values. However, according to the differences in scores on the Visual Analogue Scale(VAS)for fatigue between, before and after administration of the study tablets, subjects in the fish meat-derived peptides group showed significantly larger decreases compared to those in the placebo group, thus implying a significant fatigue reduction in the fish meat-derived peptides group. The results of a heart rate variability(HRV)analysis using TAS9View showed no significant differences or trends in any of the values. Conclusion This study demonstrated that the oral intake of fish meat-derived peptides safely alleviated fatigue in humans. However, no objective data showing fatigue reduction was obtained, thus warranting further detailed investigation. UMIN-CTR(UMIN000034278) -
カプロン酸エチル含有飲料の摂取が健常成人男性の脂質代謝に及ぼす影響―プラセボ対照ランダム化二重盲検クロスオーバー比較試験―
48巻8号(2020);View Description Hide DescriptionObjectives To evaluate the effects of single intake of a beverage containing ethyl caproate (IUPAC name: ethyl hexanoate)on lipid metabolism among healthy adult males. Methods The placebo-controlled, randomized, double-blinded, crossover study was conducted among 40 healthy adult males. The subjects consumed a beverage containing 50μg of ethyl caproate or a placebo, and then respiratory metabolism was measured at rest for 30 minutes in a sitting position and during exercise for 30 minutes using an ergometer(30 W, 60 rpm). The respiratory quotient(RQ)was the primary endpoint, and lipid oxidation level and energy expenditure(EE)were the secondary endpoints. Results The resting RQ in the sitting position was significantly lower in the group that consumed the ethyl caproate-containing beverage than in the group that consumed the placebo beverage(P<0.05). Furthermore, the resting lipid oxidation level in the sitting position was significantly higher in the group that consumed the ethyl caproate-containing beverage than in the group that consumed the placebo beverage(P<0.05). By contrast, there was no significance on RQ or lipid oxidation levels during exercise, or on EE either at rest in the sitting position or during exercise. Conclusions Single intake of a beverage containing ethyl caproate increased the proportion of lipids consumed by energy production at rest in the sitting position, indicating that this beverage promote lipid metabolism in sedentary lifestyles, such as desk work. Thus, these findings demonstrate the utility of this beverage as a functional food to assist in lipid metabolism. (UMIN ID:UMIN000039405) -
Relieving Effects of Bovine Milk—derived Alpha—lactalbumin on Menstruation—related Symptoms in Healthy Women Volunteers―A Randomized, Double—blind, Placebo—controlled Crossover Study―
48巻8号(2020);View Description Hide DescriptionBackground In women of reproductive age, menstruation-related symptoms such as menstrual pain and premenstrual syndrome are sometimes associated with health problems. Bovine milk-derived alpha-lactalbumin(αLA)has the potential to moderate menstrual-related symptoms. Objectives We evaluated the effects of αLA on menstrual-related symptoms of healthy women. Methods A randomized, double-blind, placebo-controlled, crossover study of the effects of αLA was performed in 55 healthy Japanese women. The subjects received 900 mg of αLA (per day)or a placebo from the 8th day after their last menstrual period started to 4th day of their next menstruation. The menstrual distress questionnaire(MDQ)was used to assess the subjectsʼ premenstrual period and menstrual period symptoms. A visual analog scale for menstrual pain was administered during the first four days of menstruation. Results Our results revealed that the subjectsʼ physical symptom score on the MDQ during their menstrual periods was significantly reduced by αLA treatment compared to the placebo. The improvement in the feeling of exhaustion after αLA intake was significant at both menstruation and premenstruation. No treatment-related side effects were observed. Conclusions The results indicate that αLA can have a beneficial effect by lessening the feeling of exhaustion and other physical symptoms related to menstruation(. UMIN Clinical Trials Registry ID: UMIN000037316) -
Effect of Camellia japonica Seed Extract on Peripheral Body Temperature―A Randomized Double—blind Placebo—controlled Crossover Trial―
48巻8号(2020);View Description Hide DescriptionObjectives The aim of this study was to examine the efficacy of Camellia japonica seed extract(CJE)supplement on skin temperature after cooling-load in healthy Japanese with cold sensitivity. Methods A randomized, placebo controlled, double-blind, crossover study was conducted for 24 healthy volunteers(aged from 20 to 64 years)with cold sensitivity. Subjects consume either placebo or CJE(300 mg)for 2 weeks. Then, after consuming each sample, the skin temperature was measured 0 to 30 minutes after the cooling-load. Results The change in skin surface temperature of CJE group was significantly increased compared with placebo group at 30 min after cooling-load(P<0.05). Recovery rate of skin surface temperature at 30 min after cooling load was significantly high CJE group compared with placebo group. Conclusions In conditions where people feel cold, CJE is expected to increase surface body temperature and improve various conditions accompanying cold sensations. -
Inhibitory Effect of Isomaltodextrin Intake on Increase in Postprandial Blood Triglycerides―A Randomized, Placebo—controlled, Double—blind, Crossover Study―
48巻8号(2020);View Description Hide DescriptionObjectives Isomaltodextrin(IMD)has been shown to inhibit elevation of postprandial triglycerides(TG)in healthy individuals with high postprandial blood TG levels. However, its effect has not been reported in healthy individuals with slightly high fasting TG. In this study, we examined the inhibitory effect of IMD on postprandial TG elevation in subjects with high-normal to slightly-high fasting TG levels. Methods A randomized, placebo-controlled, double-blind, crossover study was conducted in 90 subjects with fasting TG levels ≥120 mg/dL and <200 mg╱dL. The subjects were given a high︱fat diet(43.2 g fat)together with drinking water prepared by dissolving a test food containing IMD(5 g dietary fiber)or placebo food lacking IMD. Blood samples were collected before and 2, 3, 4, and 6 hours after intake of the high-fat diet to assess blood lipid parameters. Results In the 80 subjects analyzed, the area under the curve of TG after intake of the high-fat diet with the test food containing IMD was significantly lower than that for the placebo food. Furthermore, TG and Remnant-like Lipoprotein particle cholesterol(RLP-C)levels for the test food group also showed significant decreases compared to the placebo food group. Similar results were seen in a sub-group analysis of subjects with fasting TG levels of <150 mg╱dL(n=51). Conclusions Intake of IMD inhibited increases in postprandial blood TG and RLP-C in subjects with high-normal to slightly-high fasting TG levels. Intake of IMD also had a similar effect for subjects with normal fasting TG levels. (UMIN000038037) -
健常成人に対する小麦由来グルタミン含有ペプチド摂取による運動負荷後の疲労感軽減効果―プラセボ対照ランダム化二重盲検クロスオーバー比較試験―
48巻8号(2020);View Description Hide DescriptionObjectives This study aimed to evaluate the effect of wheat glutamine-containingpeptides on the fatigue after exercise, using a randomized, double-blind, placebo-controlled, crossover comparative method. Methods Twenty healthy volunteers ranging in age from 20 to 65 received glutamine-rich peptides(not less than 4.2 g)or a placebo daily for 8 days. Participants performed an exercise using a bicycle ergometer for 60 min, just before and 8th day during the intake period. The visual analogue scale(VAS)for fatigue feeling, the rating of perceived exertion (RPE)and the profile of mood states(POMS)were recorded before and after the exercise. What is more, the blood levels of TGF-β, CK, glutamine and branched-chain amino acids(BCAA)were measured after the exercise. Results Although there were no significant differences between groups in the VAS, RPE, POMS and the blood-CK level, the blood-TGF-β level in the test group was significantly lower than those of the placebo group after the intake period. In addition, the blood levels of glutamine and BCAA in the test group were significantly higher than those of the placebo group after the intake period. Concerning participants equipped with high endurance, the VAS for fatigue feeling after their exercises for 60 min significantly improved compared to that of the placebo group after the intake period.Conclusions The intake of wheat glutamine-containing peptides were demonstrated to reveal improvement effects of the fatigue feeling after exercise stress.(UMIN000038134) -
グルコサミン含有食品の膝関節に対する有効性および安全性の検討―プラセボ対照ランダム化二重盲検並行群間比較試験―
48巻8号(2020);View Description Hide DescriptionObjectives The study aimed to verify the efficacy on knee joint and safety of dietary supplement containing Glucosamine derived from Crustacean. Methods A placebo-controlled, randomized, double-blind, parallel-group study was conducted for 40 participants orally intaked dietary supplement containing 1688 mg of Glucosamine or placebo for 12 weeks. Japanese Knee Osteoarthritis Measure (JKOM)and Japanese Orthopaedic Association(JOA)score were used for evaluation of knee joint function. Results The JKOM scores were significantly improved between dietary supplement and placebo after 12 weeks, but not the JOA scores. Side effects related to intake of Glucosamine were not confirmed on this study. Conclusion These results strongly suggest that the dietary supplement containing Glucosamine can provide some degree of pain relief and improved knee joint function. UMIN ID:UMIN000035251
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BRIEF COMMUNICATION
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細菌性髄膜炎治療におけるセフトリアキソンの先発品と後発品の治療学的同等性を検討する後ろ向き観察研究
48巻8号(2020);View Description Hide DescriptionObjectives Bacterial meningitis is recognized as a neurologic emergency. Ceftriaxone (CTRX), a third-generation cephalosporin, is used for the treatment of bacterial meningitis as an empiric therapy. Although generic medicines(GM)containing CTRX are widely used for pharmacotherapies, there are few reports comparing the therapeutic equivalence of original medicines(OM)and GM. This study aimed to compare the efficacy and safety of OM and GM of CTRX in patients with bacterial meningitis. Methods Patients aged over 18 years with bacterial meningitis, which were given intravenous CTRX(4 g/day)for at least 5 days, were included to the study between January 2016 and December 2018 at Juntendo University Hospital(1051-bed university hospital). Results The number of patients treated with OM and GM containing CTRX was both five, and their median age was 39(28-85)and 47(26-72)years, respectively. Median duration of OM and GM administration was 7(6︱11)and 11(5︱33)days, respectively. No exacerbation of meningitis symptoms during treatment of both medicines containing CTRX was observed. Also, no statistical differences in the ratio of laboratory values before and after administration of between OM and GM was confirmed. Furthermore, no adverse events which is suspicious to be caused by them, leading suspension of administration, was observed. Conclusions These results suggested that GM containing CTRX is therapeutic equivalent to OM on the treatment of bacterial meningitis. These results are also expected to help promote the use of generic medicines.
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COLUMN
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INFORMATION
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