薬理と治療
Volume 41, Issue 3, 2013
Volumes & issues:
-
扉・目次
-
-
-
BOOK PREVIEW
-
-
【臨床研究を適正に評価するにはDr. ファーバーグが教える26 のポイント】 <第1 回>ランダム化比較試験の長所は何か?
41巻3号(2013);View Description Hide Description
-
-
ROUNDTABLE DISCUSSION
-
-
臨床課題を鑑みた高齢者糖尿病の治療戦略─認知症(第7の合併症)の発症抑制を目指す血糖管理のあり方─
41巻3号(2013);View Description Hide Description想像する以上に急増する認知症。その重大なリスクのひとつに糖尿病がある。認知機能低下は血糖管理不良と低血糖リスクの両者が懸念され,それらがまた,認知機能低下を進行させる。この悪循環を断ち切るためには,どのような治療が必要か,熱い討論を交わしていただいた。 -
臨床課題を鑑みた高齢者糖尿病の治療戦略―糖尿病性認知症(第 7 の合併症/3 型糖尿病)への挑戦―
41巻3号(2013);View Description Hide Description「糖尿病の第 7 の合併症」と言われる認知機能低下/認知症。認知機能の低下は血糖管理を困難にし,それによる低血糖や血糖管理不良が,認知機能の低下を促進する。この悪循環を形成させないためには,どのような糖尿病治療が高齢者に必要なのか,熱く討論していただいた。
-
-
REVIEWS
-
-
関節リウマチに対するトシリズマブの臨床的意義―最近の知見―
41巻3号(2013);View Description Hide DescriptionInterleukin 6(IL-6)is a key cytokine in the pathogenesis of rheumatoid arthritis(RA).Tocilizumab(TCZ)is a humanized, anti-human IL-6 receptor monoclonal antibody that originated in Japan and inhibits IL-6 from binding with the IL-6 receptor. Clinical trials of TCZ in RA patients have demonstrated that TCZ improved signs and symptoms, relieved structural damage, and improved quality of life compared to the control groups. TCZ was first approved in Japan in 2008, in the EU in 2009, and in the US in 2010. Standard treatment regimen with TCZ in Japan is 8 mg/kg intravenously(TCZ-IV)every 4 weeks. A subcutaneous form of TCZ(TCZ-SC)is being developed. The MUSASHI study in Japan showed that the efficacy of TCZ-SC at 162 mg/body per 2 weeks was equivalent to the efficacy of TCZ-IV at 8 mg/kg per every 4 weeks IV. Effectiveness of TCZ has been demonstrated in clinical practice as well in clinical studies conducted prior to launch. Although anti-tumor necrosis factor(anti-TNF)drugs were more effective when combined with methotrexate(MTX)than anti-TNF monotherapy, many clinical studies, including the ACT-RAY study, found the efficacy of TCZ in monotherapy to be nearly equivalent to TCZ+MTX. The safety profile of TCZ has been clarified by clinical studies, including long term extension studies and all case post-marketing surveillance (PMS)conducted in Japan. The most common adverse events(AE)and serious AE were infections. The incidence rate of serious infection was similar to that reported in clinical studies and PMS for anti-TNF drugs. -
トシリズマブとトファシチニブのシグナル伝達阻害の差異について
41巻3号(2013);View Description Hide DescriptionRheumatoid arthritis(RA)is a chronic inflammatory autoimmune disease resulting in progressive joint destruction and polyarticular synovitis. A major cause of pathogenesis is thought to be TNF-α, IL-1, and IL-6 inducing activation and infiltration of inflammatory cells, proliferation of synovial lining cells, angiogenesis, and destruction of cartilage and bone. This review discusses the difference in the modes of action of IL-6 and JAK in the signaling cascade of inflammatory cytokines. Tocilizumab is an IL-6 receptor blocker that has been demonstrated in the actual clinical setting to be useful in preventing symptoms of RA, improving activities of daily living, and inhibiting structural damage of joints. Its mode of action involves blocking only IL-6R-gp130 signaling, resulting in the activation of intracellular JAK1 and JAK2, which has a variety of pathophysiological effects in RA pathogenesis. Tofacitinib, a JAK1 and JAK3 inhibitor with short plasma half-life(T1/2=3 h), shows high efficacy comparable to that of biologics such as TNF-α inhibitors, through inhibiting the intracellular signaling of various cytokine receptors, such as IFN-α/γ receptors, gp130, and common γ chain. JAK plays an important role in the immune system and hematopoietic system by modulating cell proliferation, survival, differentiation, and activation. At present, it is not clear whether FDA-approved doses of tofacitinib inhibit joint destruction in established RA. Possible complications, including anemia, myelosuppression, immunosuppression, NK cell depletion, and tumorigenesis, should be carefully examined, especially in Japanese patients. Its clinical use should be managed with caution until clinical evidence and tolerability has been established.
-
-
ORIGINAL ARTICLES
-
-
関節リウマチ患者を対象としたトシリズマブ皮下投与時の疼痛評価―トシリズマブ皮下注製剤と生理食塩液の比較―
41巻3号(2013);View Description Hide DescriptionObjective The objective of this study is to assess pain during the subcutaneous injection of tocilizumab(TCZ-SC)using physiological saline as the control in patients with rheumatoid arthritis. Method Either TCZ-SC(81 mg or 162 mg/2 weeks)or saline at corresponding volumes was injected at a 5-min interval to the right or left abdominal part of total 20 patients with rheumatoid arthritis. Immediately after each injection, the pain at the injection sites was assessed by order and using Wong-Baker Face Pain Rating Scale(FS)and visual analog scale(VAS). Results Twenty patients (8 in 81 mg dose group and 12 in 162 mg dose group)were included in this study. No difference was observed in pains at the injection sites of TCZ-SC and saline expressed by injection order, FS scores and VAS;thus in the analysis of injection order, patients who felt pain more in TCZ-SC were 50% in the 81 mg dose group and 58.3% in 162 mg dose group. In the analysis of variance of FS scores, the average values(95% CI) of the difference between TCZ-SC and saline were 0.00(-1.60 to 1.60)in the 81 mg dose group and 0.33(-0.49 to 1.16)in the 162 mg dose group. In the analysis of variance of VAS, the average values(95% CI)of the difference between TCZ-SC and saline were -12.4 mm (-40.5 to 15.8 mm)in the 81 mg dose group and 7.9 mm(-13.2 to 29.1 mm)in the 162 mg dose group. Conclusion Since there was not observed significant difference in pain at the injection sites between TCZ-SC groups and saline group, high adherence of injection can be expected for the present TCZ-SC. -
フィルグラスチムバイオ後続品 TKN732 と市販製剤グランとの薬物動態比較試験
41巻3号(2013);View Description Hide DescriptionBackground Filgrastim is used for medical treatment of neutropenia and for hematopoietic stem cell mobilization. Three pharmacokinetic(PK)studies were conducted to compare the PK and pharmacodynamic(PD)profiles of TKN732, a filgrastim biosimilar, with filgrastim Gran, marketed in Japan. TKN732 is manufactured from the same active pharmaceutical ingredient as XM02 which is approved by EMA and FDA. Methods The PK studies were randomized, single-dose, two-period crossover, two-arm studies with a three-week wash-out period. In total, 80 healthy male subjects were enrolled, 30 in each of two subcutaneous administration studies and 20 in an intravenous administration study. Subjects were randomized and received a single dose of the test drug(TKN732)or the reference drug(Gran syringe, Kyowa Hakko Kirin Co., Ltd.), with subsequent crossover. The serum rhG-CSF concentrations were measured by enzyme-linked immunosorbent assay(ELISA)for 48 hours after injection. The absolute neutrophil counts(ANC)were determined with a Coulter automated hematology analyzer. The primary PK(AUC0-48h and Cmax)variables were considered equivalent if the 90% confidence intervals were in the range of 80-125%. Equivalence of the secondary PD(ANC AUEC0-96h and ANCmax)variables was evaluated on the basis of the 95% CIs. Results Seventy-six subjects completed the studies. Statistic equivalence between the two products was demonstrated for both the PK and PD parameters in each study. The incidence of adverse events was the same with the two drugs, and they were both well tolerated. Conclusion The study results demonstrated the equivalence of TKN732 and the reference drug, Gran, with respect to their PK, PD and safety profiles. -
フィルグラスチムバイオ後続品 TKN732 と市販製剤グランとの薬力学比較試験
41巻3号(2013);View Description Hide DescriptionBackground Filgrastim is used for medical treatment of neutropenia and for mobilization of hematopoietic stem cells. Two pharmacodynamic(PD)studies were conducted to compare the PD profiles of TKN732, a filgrastim biosimilar, with filgrastim Gran syringe, marketed in Japan. TKN732 is manufactured from the same active pharmaceutical ingredient as XM02 which is approved by EMA and FDA. Methods PD-SC300 single-dose study was performed to examine the equivalence of the effects of the drugs in increasing the neutrophil count. It was a randomized, single-blind, two-period, cross-over, two-arm study with a three-week wash-out period. Thirty-six healthy male subjects were randomized and received a single subcutaneous dose of 300 μg/body of TKN732 or Gran syringe, with subsequent crossover. The absolute neutrophil counts(ANC)were determined with an automated hematology analyzer. The primary PD (ANC AUEC096h and ANCmax)variables were considered equivalent if the 95% confidence intervals were in the range of 80-125%. PD-SC300 repeated-dose study was performed to examine the equivalence of the drugs in mobilizing hematopoietic stem cells. It was a randomized, single-blind, two-period, crossover, two-arm study with a 23-day wash-out period. Sixty healthy male subjects were randomized and received five daily subcutaneous doses of 300 μg/body/day of TKN732 or Gran syringe, with subsequent crossover. The CD34-positive cell count(CD34+)in the peripheral blood was determined by single-platform flow cytometry assay. Equivalence of the primary PD(CD34+ AUEC0144h and CD34+max)variables was assessed as in the single-dose study. Results Thirty-five subjects completed the PD-SC300 single-dose study, and 56 subjects completed the PD-SC300 repeated-dose study. Statistic equivalence between the two products was demonstrated for the PD parameters in each study. The incidence of adverse events was the same with the two drugs. TKN732 was well tolerated, with no additional safety concerns compared with Gran. Conclusion The study results demonstrated the equivalence of TKN732 and the reference drug, Gran, in terms of their PD and safety profiles. -
薬物療法受療中の高齢 2 型糖尿病患者の食習慣と血糖値との関係
41巻3号(2013);View Description Hide DescriptionIn this study, relationship between dietary habits(skipping a meal, having a light meal or snack)and blood glucose level and hypoglycemia in elderly type 2 diabetes was examined. Among the 139 patients, 12% skipped a meal and 86% had a light meal and/or snack. Incidence rate of hypoglycemia was significantly higher in patients who skipped a meal(41.2% vs. 18.9%;p<0.05)and was also higher in patients treated with SU agents(27.6% vs. 12.7%;p<0.05). HbA1c level was significantly higher in patients who had both a light meal and snack(7.3% vs. 6.8%:p<0.01)and in such patients, HbA1c level was significantly lower in those treated with DPP-4 inhibitors(7.0±0.8% vs. 7.7±1.1%;p<0.01). It is important to understand the dietary habits and to determine the appropriate drug therapy, to provide an effective and safe treatment for elderly type 2 diabetes. -
青森県産ニンニクエキス含有食品が勤労者のストレス,睡眠の質,疲労および生活の質に及ぼす効果
41巻3号(2013);View Description Hide DescriptionObjective The aim of this study was to evaluate the effectiveness of the Aomori garlic extract-containing dietary supplement on stress, fatigue, sleep, and quality of life(QOL). Methods Seventeen active workers who had subjective symptoms with insomnia and lassitude were enrolled in an open-labeled study in which self-assessed stress, fatigue, and sleep, as well as biomarkers including serum dehydroepiandrosterone sulfate(DHEA-S)and salivary cortisol awakening response, were evaluated following intake of the Aomori garlic extract-containing dietary supplements for up to 8 weeks at a daily dose of 500 mg. Results Athens Insomnia Scale(AIS)and the Japanese version of the Pittsburgh Sleep Quality Index(PSQI-j)were significantly improved, from 12.8 to 5.7 and from 9.4 to 5.6, respectively, 8 weeks after test supplemet intake. The Profile of Mood States Short Form Japanese version(POMS-S), which measures subjective psychological states, and the quality of life score significantly improved during test supplement intake. Blood DHEA-S, which inversely correlates stress, increased significantly at the 4th week, and the DHEA-S/corticol ratio showed a trend of increase during test supplement consumption. Conclusions The consumption of the Aomori garlic extract-containing dietary supplements is suggested to improve subjective quality of sleep, negative mental mood, fatigue, and QOL. -
高分岐デキストリン,パラチノース,トレハロース配合濃厚流動食の食後血糖値への影響―ラットに対する単回投与試験―
41巻3号(2013);View Description Hide DescriptionRecently, the patients that decreased renal function and abnormal glucose tolerance have been increasing with rapid aging. Since it corresponds to such a case, the liquid diet in which digestion is gradual and the blood glucose level does not rise easily in consideration of the burden on the renal disorder is demanded. Then, in the liquid diet which decreased the content of protein, Na, K, and P, we investigated the effect of carbohydrate on blood glucose level transition in rat by the difference in the combination of palatinose, trehalose, and high branched dextrin as a source of carbohydrates. As a result of examination, when the percentage to all the carbohydrates are palatinose 40%, trehalose 20% and high branched dextrin 40%, as compared with the liquid diet containing dextrin(DE:10-12), it became clear that the blood glucose level after administration shows a low value significantly. These results suggest that the application to the renal disease patient who has abnormal glucose tolerance, such as diabetic nephropathy, is expected.
-