薬理と治療

Volume 46, Issue 4, 2018
Volumes & issues:
-
扉・目次
-
-
-
TOPICS 第17回CRCと臨床試験のあり方を考える会議 2017 in 名古屋
-
- シンポジウム1/院内コーディネーションのコツここにあり!~専門性を活かしたチームの取組み~
-
-
-
-
ORIGINAL ARTICLES
-
-
高い安全性を求めた新規SPPARMα製剤の出現は何をもたらすのか―エビデンス検証の可能性と医療経済学的考察―
46巻4号(2018);View Description
Hide Description
Background Hypertriglyceridemia is a risk factor for atherosclerotic diseases. Fibrates have been used for a long time as therapeutic agents for hypertriglyceridemia, but sufficient evidence for prevention of cardiovascular events has not been demonstrated. In addition, the benefits of new selective PPARα modulator(SPPARMα), pemafibrate compared to conventional fibrates such as fenofibrate have not been clarified. Methods We examined the possibility of the reduction of the cardiovascular event by pemafibrate in the PROMINENT trial, based on the results obtained from the preceding clinical trials. We also estimated lifetime cost︱effectiveness of treatment with hypertriglyceridemia by pemafibrate and fenofibrate by establishing a Markov model that estimates the lifetime prognosis of hypertriglyceridemic patients. Results Because the characteristic of patients being incorporated into the study are limited and the rate of discontinuation due to side effects of medication is small, it is highly likely that in the PROMINENT trial, MACE suppression of type 2 diabetic patients with hypertriglyceridemia would be demonstrated. In the health economics evaluation, it is shown that pemafibrate is a drug with superior cost benefit compared to fenofibrate, due to the low discontinuation rate of treatment by adverse effect related to liver and kidney. Conclusion Pemafibrate has excellent cost benefit which is expected to reduce cardiovascular events in type 2 diabetic patients accompanied by hypertriglyceridemia with less hepatic and renal adverse events leading to treatment discontinuation. -
2 型糖尿病患者を対象としたジペプチジルペプチダーゼ—4 阻害薬テネリグリプチンの単独療法および糖尿病治療薬との併用療法における安全性と有効性―特定使用成績調査(RUBY)の中間報告―
46巻4号(2018);View Description
Hide Description
Objective Safety and efficacy of the dipeptidyl peptidase-4 inhibitor teneligliptin were examined in clinical practice by post-marketing surveillance(RUBY)in patients with type 2 diabetes mellitus(T2DM)in monotherapy and combination therapies. Method Interim analysis was conducted based on case report forms collected by June 28, 2017 in RUBY surveillance in Japanese patients with T2DM who started administration of teneligliptin. We analyzed safety by the number of concomitant antihyperglycemic agents for combination therapy, and the safety and efficacy of teneligliptin in add-on therapy with prior antihyperglycemic agents. Results The number of subjects in safety analysis set was 10,532. Compared to the teneligliptin monotherapy group, as the number of concomitant drugs increased, the incidence of adverse drug reactions(ADRs), including hypoglycemia, was higher. The incidence of ADRs was 2.24% in monotherapy and 4.13% in add-on therapy with biguanides(BG), 1.57% with sulfonylureas(SU), 4.44% with α︱glucosidase inhibitors(α︱GI), 2.06% with thiazolidines (TZD), 2.47% with insulin, 2.29% with BG+SU, 1.27% with SU+α‒GI, and 1.19% with SU+TZD. The profile of ADRs was not deviated in any combination. HbAlc levels decreased significantly until 2 years after administration(-0.90%±1.23% after 2 years)in monotherapy and also similarly decreased in all combination groups. Conclusion It is considered that careful management to avoid ADRs, including hypoglycemia, are required when teneligliptin is used in combination with multiple antihyperglycemic agents. On the other hand, teneligliptin was generally well‒tolerated and improved glycemic control in monotherapy and add‒on therapies to 1 or 2 frequently use antihyperglycemic agents. -
2 型糖尿病患者におけるナトリウム—グルコース共輸送体2 阻害薬カナグリフロジンの単独療法および糖尿病治療薬との併用療法における安全性と有効性―カナグル錠100 mg 特定使用成績調査(長期使用に関する調査SAPPHIRE)の中間報告―
46巻4号(2018);View Description
Hide Description
Objectives Safety and efficacy of canagliflozin were assessed by post-marketing surveillance, SAPPHIRE, in Japanese type 2 diabetes mellitus(T2DM)patients in monotherapy and combination therapy with other antidiabetic agents. Methods Interim analysis was conducted for subjects in which surveillance forms were collected from December 2014 to September 2017. To examine the effect of concomitant use with other antidiabetic agents, we analyzed safety by the number of concomitant antidiabetic agents at the start of canagliflozin administration. In addition, safety and efficacy were analyzed for add-on treatment of canagliflozin to pretreatment antidiabetic agents that were continuously used from one month. Results The incidence rate of adverse reactions was 6.22%(n=11,479)in safety analysis set. As the number of concomitant agents increased, the incidence of adverse reactions was higher. In the analysis of safety of canagliflozin in monotherapy and add︱on therapies with one or two frequently used pretreatment agents, the profile of adverse reactions was not deviated in any combination, and there were no additional safety concerns. The change in HbA1c from baseline at 6 months of administration was -0.79%(n=7577)in efficacy analysis set. In add‒on therapies with one or two pretreatment agents, HbA1c was also decreased as compared with before administration of canagliflozin. Conclusion As the incidence of adverse reactions increased, more careful administration and observation are needed in using many agents. However, in canagliflozin monotherapy and combination with 1 or 2 pretreatment agents, there were no additional safety concerns, and the reduction of HbA1c was confirmed. -
Safety Evaluation of a Food Containing Salmon Nasal Cartilage—derived Proteoglycan (Proteoglycan F)―A Single—dose Toxicity Study in Rats―
46巻4号(2018);View Description
Hide Description
Proteoglycans(PG), as well as collagen and hyaluronic acid, are contained in large amounts in connective tissues, such as cartilage and skin, as important components of the extracellular matrix. Recently, a method for extracting PG from salmon nasal cartilage using acetic acid solution was developed, and salmon nasal cartilage-derived proteoglycan(SPG)has been reported to have anti-inflammatory and joint-protective effects. However, no single-dose toxicity studies of SPG have been reported yet. Therefore, we conducted a single-dose toxicity study by forced oral administration of a food containing salmon nasal cartilage-derived proteoglycan(Proteoglycan F)(5000 mg╱kg body weight, 1000 mg╱kg body weight as SPG) to Wistar-Hannover╱Rcc rats- the animals did not die and showed no loss of body weight during the study period, and gross pathological examination revealed no abnormalities after the study period. The results suggested that the lethal dose of proteoglycan F is higher than 5000 mg ╱kg body weight in male and female rats. -
Antihypertensive Effect of the Casein—derived Peptide Met—Lys—Pro in Individuals with High—normal Blood Pressure or Grade 1 Hypertension―A Randomized, Double—blind, Placebo—controlled, Parallel—group Trial―
46巻4号(2018);View Description
Hide Description
Background High blood pressure is a risk factor for the development of cardiovascular disease. Our previous study confirmed that the casein-derived peptide Met-Lys-Pro(MKP) inhibited angiotensin-converting enzyme in vitro and exerted an antihypertensive effect in spontaneously hypertensive rats. The aim of this study was to assess the antihypertensive efficacy of MKP in individuals with high-normal blood pressure or grade 1 hypertension. Methods A total of 120 subjects with high-normal blood pressure or grade 1 hypertension participated in this randomized, double-blind, placebo-controlled, parallel-group trial. Subjects were randomly allocated to the MKP group(n=60)or the placebo group(n=60). The MKP group received 2 capsules daily, each containing 50μg MKP, while the placebo group received 2 sodium caseinate capsules containing no detectable MKP. Blood pressure and brachial -ankle pulse wave velocity after administration were compared to baseline values. Adverse events and side effects were recorded throughout the study. Results A total of 103 subjects completed the study. Systolic blood pressure(SBP)was significantly lower than baseline after 12 weeks of MKP administration and 2 weeks post-treatment, while there were no such differences in the placebo group. The change from baseline SBP in the MKP group at 12 weeks was significantly larger than in the placebo group(P=0.017). No serious adverse events due to MKP ingestion were observed. Conclusions Daily MKP treatment can safely lower mildly elevated blood pressure. -
ビワ葉と緑茶三番茶葉を混合揉捻して製造した発酵茶葉長期摂取の内臓脂肪低減効果―ランダム化二重盲検プラセボ対照並行群間比較法―
46巻4号(2018);View Description
Hide Description
Objectives We developed a new fermented tea by mixing loquat leaves and third crop green tea leaves at the level of 1:9. We investigated the effects of feeding fermented tea leave powder for 8 weeks on visceral fat in healthy volunteers. Methods We conducted a randomized, double-blind, placebo-controlled, parallel-group comparative study. Subjects with obese tendency(BMI: 23-30)were divided into the two groups, and were either given the test foods containing 1.05 g fermented tea leaves or placebo foods not containing fermented tea leaves. Test foods and placebo foods were mixed with water or hot water, and were given to subjects. Results Feeding fermented tea leaves induced the reduction of the area of visceral fat, and the effect was especially strong in subjects under 60 years old. The suppression of visceral fat is possible to be exerted through the drop of lipase activity. The enzyme activity was inhibited by gallate-type catechins and catechin polymerized polyphenols. Conclusions These results suggested that the fermented tea leaves made from loquat leaves and green tea leaves has the effect to reduce visceral fat. -
Lactobacillus brevis NTT001 含有チョコレートの腸内環境改善効果―ランダム化プラセボ対照二重盲検クロスオーバー試験―
46巻4号(2018);View Description
Hide Description
Objectives The aim of this study was to evaluate the effect of intake of Lactobacillus brevis (L. brevis)NTT001 on the intestinal environment. Methods Twenty two healthy volunteers with a tendency for constipation were enrolled in a randomized double-blind placebo-controlled crossover trial. The volunteers were given 28 g of test chocolate containing live L. brevis NTT001(1.0*109 cfu╱28 g)or placebo chocolate daily for two weeks, each separated by a 2-week washout period. After intake, the number of fecal Lactobacillus and Bifidobacterium, the amounts of fecal organic acid, the amount of metabolic products such as indole and ammonia, fecal microbiota, and questionnaire (defecation frequency, fecal shape, and others)were measured. Results The number of fecal Lactobacillus was significantly increased after ingestion of test chocolate compared with placebo, but the amounts of fecal organic acid including acetate were not change during experiment. Furthermore, the amount of indole in the feces was significantly decreased after the intake of test chocolate. With regard to microbiota, the ratio of Holdemania was significantly decreased, and the ratio of Ruminococcus tended to be increased after ingestion of test chocolate compared with placebo. Compared to before ingestion period, defecation frequency and defecation days were significantly increased throughout ingestion period by test chocolate and placebo, but no significant difference between test and placebo. Conclusions In conclusion, intake of L. brevis NTT001(1.0*109 cfu╱day)improve the intestinal environment by increase of Lactobacillus and decrease of indole in the intestine. -
Effects of Sanchi ginseng Extract on the Sexual Function in Japanese Men―A Randomized, Double—blind, Placebo—controlled, Parallel—group Trial―
46巻4号(2018);View Description
Hide Description
Objectives This study aims to investigate the effects of consuming Sanchi ginseng(Panax notoginseng)extract capsules on male libido in a randomized, double-blind, placebo-controlled, parallel-group trial. Methods In this study, we enrolled 44 healthy Japanese adult men with low libido, low erectile function domain scores on the International Index of Erectile Function(IIEF), and who fulfilled the inclusion criteria set by the physician. We randomly assigned all participants to either the intervention or the placebo group(n=22 each), and each participant consumed one capsule per day for 12 weeks of the appropriate treatment. We assessed libido at 0, 4, 8, and 12 weeks after ingestion using the IIEF, free testosterone and high-sensitivity prostate-specific antigen(hs-PSA)concentrations, nocturnal penile tumescence, the Androgen Deficiency in the Aging Male(ADAM)questionnaire, and the visual analogue scale of fatigue(VAS-F). In addition, we evaluated the safety of test foods. Results The intervention group revealed a significant elevation in the satisfaction domain score on the IIEF and prevented an increase in the hs-PSA concentration. The ADAM questionnaire analysis revealed the reduction of subjective symptoms associated with low libido. In addition, the pre- and post-sleep penile circumference significantly increased 9 and 10 weeks after ingestion(P=0.025, 0.027, 0.04, and 0.021, respectively). We observed no adverse events. Conclusions The consumption of Sanchi ginseng extract capsules for 12 weeks increases and maintains libido in healthy Japanese adult men with low libido. Furthermore, the ingestion of Sanchi ginseng capsules is safe under the conditions examined. -
高濃度水素水の日常作業および精神作業負荷による疲労に対する軽減効果
46巻4号(2018);View Description
Hide Description
Objectives In 2007, the first report that hydrogen removes active oxygen was published, and many clinical and non-clinical studies have since been conducted using hydrogen gas or water. Several diseases and symptoms are related to active oxygen, and fatigue is also induced by increases in oxidative stress. The current randomized, double-blind, placebo-controlled, crossover study was conducted to investigate the effects of hydrogen-rich water(HRW)on attenuating fatigue induced by daily activities or mental tasks. Methods Twenty-four healthy volunteers were randomized to either oral administration of hydrogen-rich water containing 0.36 mg of hydrogen or placebo for 4 weeks. Subjective sensation and work efficacy were examined using the visual analogue scale(VAS)and the advanced trail making test(ATMT), respectively, to evaluate the anti-fatigue effects of hydrogen-rich water. In addition, we measured serum malondialdehyde-modified low density lipoprotein (MDA-LDL)and derivatives of reactive oxygen metabolites(d-ROMs)as possible mechanisms of action. Results On the VAS, the hydrogen-rich water group had a significantly lower sleepiness and tension score after 4-week administration, and a significantly higher motivation and relaxation score after mental tasks compared with the placebo group. On the ATMT, hydrogen-rich water significantly reduced the mean reaction time during mental tasks. The serum MDA-LDL level after 4-week administration was significantly lower compared with before administration in the hydrogen-rich water group. The serum d-ROM level was significantly correlated with the VAS fatigue sensation score in the hydrogen-rich water group. Conclusions These results suggest that hydrogen-rich water improves several subjective sensations accompanying fatigue induced by daily activities and mental tasks by enhancing work efficacy and attenuating fatigue during mental tasks. We consider these effects to be caused by the antioxidant action of hydrogen. -
ココア摂取が高齢者におけるウォーミングアップの効果に及ぼす影響―プラセボ対照二重盲検クロスオーバー比較試験―
46巻4号(2018);View Description
Hide Description
Background Exercise is essential for elderly people to extend their healthy life expectancy. Prior warm-up, as a means of preparing the body to be receptive to exercise, is linked to prevention of falls and injury. Objectives The aim of this study was to clarify whether ingestion of cocoa 30 minutes before a warm-up is useful for condition-building and maintaining the effects of warm-up. Methods Ten healthy elderly volunteers participated in the trial(average age, 67.5 years; 5men and 5 women). The study had a placebo-controlled, double︱blind, crossover, comparative design. The cocoa beverage was containing 30 mg of cacao flavanols. The placebo beverage was a cocoa-flavored drink with similar nutritional composition. Physical function of long seat body anteflexion, sublingual temperature, skin surface temperature of the facies posterior cruris and the dorsal region of the foot, grip, knee joint extension strength, plantar pressure distribution, and center of gravity fluctuation track length were evaluated. The statistical analysis consisted of a one-way analysis of variance (ANOVA)and multiple comparison. Differences were considered statistical significant when P<0.05. Results The measured value of long seat body anteflexion, sublingual temperature, skin surface temperature of the facies posterior cruris and the dorsal region of the foot, grip, and knee joint extension were significantly maintain higher in cocoa ingestion than that in placebo beverage. Forward transfers of weight were also significantly more maintained in plantar pressure distribution after cocoa ingestion than that in placebo beverage. Conclusion The ingestion of cocoa in elderly people before a warm-up was found to lead to a long-term maintenance of the effects of warm-up for the physical functions. The primary reason for these effects was suggested to be improved muscle function caused by increases in body temperature and surface temperature of the lower limbs due to improved blood circulation. -
ココアがウォーミングアップ後の柔軟性に与える影響―プラセボ対照二重盲検クロスオーバー比較試験―
46巻4号(2018);View Description
Hide Description
Background and Objective In todayʼs aging societies, extending healthy life expectancy will help to prevent reduction in quality of life. While elderly people are encouraged to have proactive exercise regimes, they are also subject to the risks of falls and broken bones, making pre-exercise warm-up crucial to reduce these risks. Previous studies have confirmed the results of sustainability of the effects of a warm-up in the summertime for elderly people, when conducted 30 minutes after ingesting cocoa. Those results demonstrated significant improvements in flexibility, body temperature, muscle strength, balance function, and inhibited reductions in flexibility and muscle strength. In this study, the authors confirmed the replicability of results of previous studies and verified the significant improvement in flexibility found in the agonist muscles. This study also verified the basis for the functionality of cocoa with the aim of confirming its seasonal effect. Methods A placebo-controlled, double-blind, crossover comparative study was conducted in 10 healthy elderly people aged 64-73 years.The trial drink contained 30 mg of cocoa flavanols, while the placebo drink was a cocoa-flavored beverage with a similar taste and the same level of energy as the trial drink. Participants ingested 120 mL of their drink 30 minutes prior to a warm -up, and the effects from their warm-up were assessed using indexes of flexibility, body temperature, muscle strength, and balance function. Results Flexibility: Long seat body anteflexion was found to sustain a significantly high value(P<0.05)for 30-90 minutes following the warm-up. Flexibility in the posterior femoral and triceps surae muscles was maintained at a significantly high value(P<0.05)for 30-90 minutes and 60-90 minutes after warm-up, respectively. Body temperature: Sublingual temperature expressed a significantly high value(P<0.05) 30-90 minutes following the warm-up, while a gentle trend was found for a decrease in body temperature. Furthermore, skin surface temperature of the facies posterior cruris and dorsal region of the foot were found to sustain significantly high values(P<0.05)30-90 minutes and 60-90 minutes following the warm-up, respectively. Muscle strength: Knee joint extension strength sustained a significantly high value(P<0.05)30-90 minutes following the warm-up. Balance function: While the transfer of weight forward in plantar pressure distribution sustained significance(P<0.05)30-90 minutes following warm-up, no successively significant difference was found for center of gravity fluctuation track length. Ingestion of the trial drink was found to achieve a statistically significant improvement(P<0.05)in comparison to the placebo drink for flexibility, body temperature, muscle strength, and balance function. Conclusion The ingestion of cocoa containing 30 mg cacao flavanols by healthy elderly people before warm-ups was confirmed to significantly improve flexibility, body temperature, muscle strength, and balance function after a warm-up and to sustain its effects. -
Japanese Sake Yeast Improves Human Fatigue and Vitality―A Double—blind, Randomized Placebo—controlled Clinical Cross—over Trial―
46巻4号(2018);View Description
Hide Description
Background Sleep quality is closely associated with subjective fatigue and vitality. Recently, we found that sake yeast intake improves human sleep quality. However, it remains unclear whether sake yeast-mediated sleep improvement improves daytime subjective feelings. Objectives In this study, we investigated whether sake yeast supplementation improves daytime fatigue and vitality. Methods In a double-blind, randomized, placebo-controlled cross-over clinical study, 36 healthy adults with low sleep quality(Pittsburg Sleep Quality Index≳5) were instructed to ingest 500 mg of sake yeast powder or placebo for 4 days. The effects of sake yeast were evaluated using a visual analog scale for daytime fatigue, SF-8 health survey, and a sleep quality questionnaire. Results Daytime fatigue(P<0.01)and vitality(P=0.02)as per SF-8 were significantly improved by sake yeast ingestion. Subjective sleepiness(P=0.03)and fatigue(P=0.04)in the morning were also improved. Additionally, significant correlations between fatigue or vitality and subjective sleep quality were observed. Conclusions This clinical study demonstrated that sleep improvement mediated by sake yeast intake effectively prevents daytime fatigue and increases vitality. -
酵素分解蜂の子食品の耳鳴り症状に対する改善効果―無作為化並行群間単盲検比較試験―
46巻4号(2018);View Description
Hide Description
Objectives The aim of this study was to investigate the lowest effective dose of enzymolyzed honeybee larvae powder(EHB)on tinnitus symptoms. Methods 66 subjects with mild self-perceived tinnitus handicap participated have been recruited in this study. The subjects were allocated to ora- treatment with either 180 mg or 360 mg or 540 mg or 720 mg of EHB or 720 mg of EHB combined with γ-aminobutyric acid (GABA group), Riboflavin and Cyanocobalamin or placebo daily for 12 weeks. The level of tinnitus symptoms has been evaluated at before treatment, 1 week, 2 week, 3 week, 4 week, 8 week, and 12 week after treatment, using a visual analog scale(VAS). Results 65 subjects have completed the trial. There are significant improvements related with VAS score of tinnitus in 360 mg, 720 mg and GABA group compared with placebo group at any point in time. However, no significant differences were found in 180 mg and 540 mg group. Conclusion Our results suggest that EHB supplementation with doses of 720 mg╱day is likely to be effective for relieving of tinnitus symptoms.
-
-
NEWS
-
-
-
INFORMATION
-
-
-
臨床試験を報告するための指針−CONSORT 声明に準拠して論文を執筆するための15 項目(薬理と治療2017; 45: 339-44. より再掲載)
46巻4号(2018);View Description
Hide Description
-
-