巻号一覧
43 巻 (2012)
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43 巻, 5 号
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特集／新しい心不全治療薬
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志賀 剛2012 年 43 巻 5 号 p. 303-304
発行日: 2012/09/30
公開日: 2012/12/12
ジャーナル 認証ありPDF形式でダウンロード (145K) -
猪又 孝元2012 年 43 巻 5 号 p. 305-309
発行日: 2012/09/30
公開日: 2012/12/12
ジャーナル 認証ありHyponatremia is widely known to be one of the strong prognostic predictors for heart failure (HF). However, there are few reports on the clinical benefits of correcting hyponatremia to improve HF prognosis. Although randomized clinical trials including EVEREST have not demonstrated prognostic benefits of the vasopressin V2 receptor antagonist tolvaptan, increasing evidence suggests its novel therapeutic potential in preventing low cardiac output during decongestion through increasing serum osmolarity, especially in severe hyponatremia with extravascular volume excess. In addition to being an alternative option for HF patients with renal dysfunction resistant to loop diuretics, tolvaptan may serve as a useful therapeutic tool to prevent or minimize cardiovascular events including HF exacerbation. (Jpn J Clin Pharmacol Ther 2012; 43(5): 305-309)抄録全体を表示PDF形式でダウンロード (637K) -
福本 義弘2012 年 43 巻 5 号 p. 311-315
発行日: 2012/09/30
公開日: 2012/12/12
ジャーナル 認証ありPost-capillary pulmonary hypertension (pc-PH) is defined as mean pulmonary arterial pressure≥25 mmHg and mean pulmonary capillary wedge pressure>15 mmHg, and is classified into 2 types depending on the status of pulmonary vascular resistance (PVR) or trans-pulmonary pressure gradient (TPG) : reactive pc-PH with elevated PVR (>2. 5WU) and/or TPG (>12 mmHg), and passive pc-PH with normal PVR (≤2.5WU) and TPG (≤12 mmHg). The pathogenesis of passive pc-PH is a simple backward transmission of elevated left atrial pressure, whereas reactive pc-PH is caused by functional and/or structural changes of pulmonary arteries as a result of chronic elevation of pulmonary venous pressure. Indeed, a high prevalence of pc-PH has been reported in patients with advanced systolic heart failure, diastolic heart failure, valvular heart diseases including mitral valve disease, and advanced heart failure referred for heart transplantation. Especially, reactive pc-PH is a significant prognostic factor regardless of heart failure etiology (ischemic vs. non-ischemic) and left ventricular ejection fraction (reduced vs. preserved).
Future studies are required to clarify this issue and to develop a new therapeutic target for pc-PH. Riociguat is a novel, first-in-class oral drug that directly stimulates soluble guanylate cyclase, both independent of the endogenous vasodilator NO and synergistic with NO. Phase III clinical trials of riociguat evaluating the long-term safety and clinical effectiveness of the agent in pc-PH are on-going, which may demonstrate that riociguat is effective in patients with pc-PH. (Jpn J Clin Pharmacol Ther 2012; 43(5): 311-315)抄録全体を表示PDF形式でダウンロード (515K) -
名越 智古, 吉村 道博2012 年 43 巻 5 号 p. 317-322
発行日: 2012/09/30
公開日: 2012/12/12
ジャーナル 認証ありHeart failure is currently the leading cause of death and disability across the globe. Although significant advances in pharmacological and mechanical treatments have improved the outcome of patients with heart failure, the prognosis in such patients remains poor. At present, the optimal pharmacological treatment of heart failure targets the suppression of neurohumoral activations such as the renin-angiotensin-aldosterone system (RAAS) and/or β-adrenergic receptor signaling, as well as regulation of hemodynamics. Large clinical trials in patients with heart failure, even in those with mild symptoms, have shown that mineralocorticoid receptor (MR) antagonists used in conjunction with the current standard of care improve morbidity and mortality. Increasing evidence supports the detrimental effects of aldosterone on the cardiovascular system, mainly via its MR-dependent action, in a variety of experimental models and clinical research. Of note, these unfavorable effects are more pronounced under high sodium or glucose conditions, as we and others have reported. Moreover, the pathological significance of not only systemic but also local RAAS has attracted growing attention. Furthermore, some reports have demonstrated that MR signaling can be activated without specific ligands such as aldosterone and corticosterone. Taken together, MR signaling cascades, in their high salt and/or glucose sensitive manner, play a pivotal role in the pathogenesis of heart failure. Therefore, the usefulness of MR antagonists and their indication should be more enhanced and extended, while diet control including salt restriction remains of paramount importance in the treatment of heart failure. (Jpn J Clin Pharmacol Ther 2012; 43(5): 317-322)抄録全体を表示PDF形式でダウンロード (440K) -
辻野 健, 内藤 由朗 , 増山 理2012 年 43 巻 5 号 p. 323-330
発行日: 2012/09/30
公開日: 2012/12/12
ジャーナル 認証ありAnemia is common in patients with chronic heart failure (CHF), and an independent predictor of poor prognosis. Renal dysfunction, chronic inflammation, hemodilution, bone marrow dysfunction, and iron deficiency might contribute to the development of anemia. Many clinical trials have examined the effects of erythropoiesis-stimulating agents (ESAs) on the clinical symptoms, exercise tolerance, and prognosis of CHF patients. Several small-scale trials showed the favorable effects of ESAs. However, the largest clinical trial STAMINA-HeFT (n=319) failed to show a beneficial effect of darbepoetin α on the clinical symptoms of CHF patients. On the other hand, the importance of iron deficiency has lately attracted considerable attention as a cause of not only anemia but also exercise intolerance. We have shown that the expression of duodenal iron transporters is impaired in heart failure model rats. The largest clinical trial of intravenous iron supplementation FAIR-HF (n=459) showed improvement of clinical symptoms and exercise tolerance in CHF patients with or without anemia. Further understanding of the pathophysiology of anemia seems to be necessary for the treatment of anemia in CHF patients. (Jpn J Clin Pharmacol Ther 2012; 43(5): 323-330)抄録全体を表示PDF形式でダウンロード (512K) -
志賀 剛2012 年 43 巻 5 号 p. 331-338
発行日: 2012/09/30
公開日: 2012/12/12
ジャーナル 認証ありThe ‘funny’ current (If) was first described in sinoatrial node myocytes in 1979. This current is a mixed sodium/potassium inward current, which is activated on hyperpolarisation at voltages in the diastolic range.Increased resting heart rate (HR) is a risk factor for the development of cardiovascular events in patients with known cardiovascular disease. HR reduction by β blockers is a beneficial treatment for improving the prognosis in patients with myocardial infarction and heart failure. Therefore, HR reduction by inhibition of the If current may be a suitable therapeutic option in patients with heart failure. A novel selective If inhibitor, ivabradine, is a pure HR-lowering agent. The BEAUTIFUL trial conducted in 10,917 patients with coronary artery disease and a left ventricular ejection fraction (LVEF)<40% showed no difference between the ivabradine and placebo groups in the rate of the composite endpoint of cardiovascular death, hospitalization for acute myocardial infarction, or for new-onset or worsening heart failure. In a subgroup of patients with HR≥70 bpm, however, ivabradine reduced hospitalization for myocardial infarction and for coronary revascularization. The SHIFT trial conducted in 6,505 stable heart failure patients with a LVEF≤35% and a HR≥70 bpm demonstrated that the rate of the composite endpoint of cardiovascular mortality and hospitalization for worsening heart failure was significantly lower in the ivabradine group than in the placebo group. This study showed the importance of HR reduction with ivabradine for improving clinical outcomes in heart failure. (Jpn J Clin Pharmacol Ther 2012; 43(5): 331-338)抄録全体を表示PDF形式でダウンロード (734K)
原著
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Mayuko SOMA, Ainari KONDA, Hiroshi YOSHIDA, Shuichi KISHIMOTO, Shoji F ...2012 年 43 巻 5 号 p. 339-343
発行日: 2012/09/30
公開日: 2012/12/12
ジャーナル 認証ありAims: Little is known about the maternal-to-fetal transfer ratio of ritodrine in women who are pregnant with twins and undergoing treatment with ritodrine for threatened premature delivery. We aimed to investigate the maternal-to-fetal transfer ratio for establishing rational ritodrine therapy.
Methods: Ritodrine concentrations were measured by HPLC in maternal and umbilical venous blood samples during continuous intravenous ritodrine infusion in 14 women who were expecting dizygotic twins.
Results: The maternal concentration range of ritodrine required to maintain pregnancy was 21.8-126.0 ng/mL. Serum concentrations of ritodrine did not differ significantly between the first and second twin neonates, but the maternal-to-fetal transfer ratio was significantly lower for the first than for the second twin neonate (means±SD, range: 1.05±0.23, 0.65-1.40 vs. 1.15±0.26, 0.75-1.64).
Conclusion: The concentrations of maternal ritodrine transferred to the umbilical veins of newborn twins were essentially equal, but the transfer ratios varied significantly between the first twin and the second twin. Further studies are required to establish rational ritodrine therapy. (Jpn J Clin Pharmacol Ther 2012; 43(5): 339-343)抄録全体を表示PDF形式でダウンロード (152K) -
岩崎 麻美, 渡邉 達也 , 氏原 淳, 成川 衛2012 年 43 巻 5 号 p. 345-351
発行日: 2012/09/30
公開日: 2012/12/12
ジャーナル 認証ありWith the increasing use of overseas clinical data in clinical data packages for new drug application (NDA) in Japan, the relative amount of Japanese clinical data submitted for NDA has been decreasing. Clinical data on Japanese subjects is important for physicians to decide the course of treatment in clinical practice, and the importance of post-marketing surveillance (PMS) as a means of obtaining clinical data from Japanese subjects promptly after the launch is increasing. With the purpose to investigate measures to better utilize PMS, we examined the status of recent PMS in Japan based on review reports of new drugs as well as protocols and relevant documents of PMS conducted at Kitasato Institute Hospital.
Fifty-four of 155 new drugs had conditions for approval, which required sponsors to conduct all-case surveys for a certain period of time after launching. Along with orphan drugs, some drugs used in large patient populations were required to conduct all-case surveys. As for drugs without conditions for approval, many of their protocols stipulated collection of data of over 3000 Japanese patients. Also, some protocols required collection of additional data not necessarily essential for safety evaluation of the drugs. In order to obtain Japanese clinical data in a more precise and timely manner during PMS in Japan, we encourage sponsors and regulatory authorities to consider various specific survey designs based on the characteristics of the drug and to design less burdensome report forms for proper safety evaluation. (Jpn J Clin Pharmacol Ther 2012 ;43(5) :345-351)抄録全体を表示PDF形式でダウンロード (644K)
フォーラム
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向 祐志, 寺元 剛, 五十嵐 隆, 大森 栄2012 年 43 巻 5 号 p. 353-360
発行日: 2012/09/30
公開日: 2012/12/12
ジャーナル 認証ありIncreasing numbers of global studies in Japan are playing important roles in reducing the so-called “drug lag.” The increase in number of clinical trials with complicated protocols, including the global studies, increases the workload on clinical research coordinators (CRC). Therefore, more efficient implementation of CRC tasks is necessary. In addition, improvements are required in quality control (QC) systems in institutions conducting clinical trials, including the employment of a local data manager (LDM). We have introduced a QC system in our institution using paper checklists usually provided by the sponsors of clinical trials. However, it is difficult to prevent the occurrence of human error. Therefore, we attempted to improve the QC system by switching from paper-based to electronic checklists (e-checklist) and supplementing the content confirmation process by staff via cloud computing. The e-checklist developed by our institution is a task management tool that does not require input of source data. The CRC can enter the e-checklist by iPad when working with a subject, and the data are immediately shared between related staff of our institution via Google Docs. The results of a questionnaire survey about the operability and usefulness of the e-checklist indicated a positive evaluation for operability on the iPad. We also found that content confirmation by other staff is useful to reduce errors when the CRC works with a subject. In conclusion, this QC system is useful for institutions conducting clinical trials, especially for those without an LDM. (Jpn J Clin Pharmacol Ther 2012; 43(5): 353-360)抄録全体を表示PDF形式でダウンロード (771K)
特別寄稿
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越前 宏俊2012 年 43 巻 5 号 p. 361-364
発行日: 2012/09/30
公開日: 2012/12/12
ジャーナル 認証ありPDF形式でダウンロード (382K)
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