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Volume 46 (2015)
- Issue 6 Pages 253-
- Issue 5 Pages 225-
- Issue 4 Pages 179-
- Issue 3 Pages 115-
- Issue 2 Pages 55-
- Issue 1 Pages 3-
Volume 46, Issue 6
Displaying 1-3 of 3 articles from this issue
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Original Article
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Kenichi OGUCHI, Machiko OKAMOTO, Hitoshi IWABUCHI , Manabu ASANO2015 Volume 46 Issue 6 Pages 253-258
Published: November 30, 2015
Released on J-STAGE: December 19, 2015
JOURNAL FREE ACCESSThe present study investigated the pharmacokinetics of darbepoetin alfa (DA) after a single intravenous injection of 5 μg in 6 patients on hemodialysis. Following a washout period of erythropoiesis stimulating agents (ESA), DA at 5 μg was injected intravenously after the first dialysis session of the week. Serum concentrations of DA were measured at 8 points: before and 0.5 to 168 h after DA dosing. Serum concentrations of DA ranged from 1.9 to 3.4 ng/mL at 0.5 h, and was maintained at almost 1 ng/mL even at 24 h after DA dosing. The elimination half-life, AUC0−∞ and V0 were calculated as follows (mean±SD): 21.2±6.2 h, 68.3±10.5 ng・h/mL and 2280±770 mL, respectively. The serum concentration-time profile showed similarity with those after single intravenous injection of DA at 10 to 60 μg. Considering the serum concentrations of DA required to stimulate erythropoiesis in erythroid progenitor cells, intravenous injection of DA at a dose of 5 μg is expected to be suitable for achieving effective serum DA concentration in patients on hemodialysis with renal anemia.View full abstractDownload PDF (577K) -
Makoto YONO, Megumi KIMURA, Kazuya ITO, Yumi INOUE, Kohichiro FURUKAW ...2015 Volume 46 Issue 6 Pages 259-264
Published: November 30, 2015
Released on J-STAGE: December 19, 2015
JOURNAL FREE ACCESSObjectives: Duloxetine, a serotonin and noradrenaline reuptake inhibitor, has been approved for the treatment of stress urinary incontinence (SUI) in women in the European Union, but not in the United States or Japan where newer drugs are under development. The present urodynamic study in women with SUI was performed to evaluate the effect of duloxetine on urethral function and to determine an appropriate method for making go/no-go decisions in early clinical studies of new drugs under development for SUI treatment.
Methods: A randomized, double-blind, single-dose, two-period crossover study of 40 mg duloxetine was conducted in 10 women with SUI (≥1 episode/wk). The urethral pressure profiles at rest and during coughing, Valsalva leak point pressure, and leakage in a 20-min pad test were measured before and 6 hr after administration of duloxetine or placebo.
Results: Although a single oral dose of duloxetine did not affect Valsalva leak point pressure or leakage in a pad test, this drug significantly increased the mean and maximal urethral closure pressures at rest calculated over the entire urethra, compared with placebo. During coughing, duloxetine significantly increased the mean closure pressure and the change from baseline in maximal amplitude of negative closure pressure spike in the distal third of the urethra, compared with placebo.
Conclusions: The facilitatory effect of duloxetine on urethral closure function was confirmed in women with SUI, suggesting the usefulness of the method used in this urodynamic study. Thus, the proposed method is potentially useful to reduce attrition rate by providing decision-making data in early clinical studies of new drugs being developed for treating SUI.View full abstractDownload PDF (645K) -
Hiroshi HASEGAWA, Shigeru FURUTA, Shunji KURIBAYASHI, Minoru TSUDA, ...2015 Volume 46 Issue 6 Pages 265-272
Published: November 30, 2015
Released on J-STAGE: December 19, 2015
JOURNAL FREE ACCESSA questionnaire on conventional “human mass balance (MB) study” was sent to 61 pharmaceutical companies affiliated with the Japan Pharmaceutical Manufacturers Association in 2013, and 48 companies responded. The strategy and design of MB study were also investigated with respect to the approved new molecular entities in Japan and the US from 2002 to 2013. Most companies conduct MB study during proof-of-concept clinical trials or before phase III studies. Additionally, FDA and ICH guidance have encouraged the companies to perform MB studies routinely and/or in an earlier phase. The present survey suggests that MB study has occupied an important position in new drug development, and that implementation of the study appears to be judged carefully taking the necessity into consideration.View full abstractDownload PDF (581K)
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