Volume 37,
Issue 11,
2009
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SERIES
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「いろいろな臨床試験のケースレポート: 温泉のRCTから看護のSRまで」
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薬理と治療 37巻11号, 893-894 (2009);
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薬理と治療 37巻11号, 895-904 (2009);
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ORIGINAL ARTICLES
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薬理と治療 37巻11号, 909-930 (2009);
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To assess the safety, tolerability and efficacy of long−term treatment(52 weeks)withimidafenacin 0.2 mg twice daily in overactive bladder(OAB)patients without safety concernand with insufficient effect of imidafenacin 0.1 mg twice daily(the standard dose). The studywas a multicenter, open−label trial. Patients who met eligibility criteria entered the study andreceived treatment with imidafenacin 0.1 mg twice daily for 12 weeks, and the dose of imidafenacinwas increased(to 0.2 mg twice daily)at week 12 if the patients met the dose increasecriteria, and if not, the dose was maintained. Imidafenacin were administered for total 52weeks(in the 0.1 mg twice daily arm)or 64 weeks(in the 0.2 mg twice daily arm). A total435 patients were enrolled in the study, 182 patients(41.8%)received an increased dose of0.2 mg twice daily and 153(84.1%)of them completed a year of 0.2 mg twice daily treatment.Imidafenacin 0.2 mg twice daily treatment was safe and well tolerated. The dose increase to0.2 mg twice daily further improved the number of urge incontinence episodes per week wasat week 16(4 weeks after the dose increase to 0.2 mg twice daily). This effect was sustaineduntil week 64(52 weeks after the dose increase), when the mean percentage change frombaseline in the number of urge incontinence episodes per week was −77.85% at week 64 ordiscontinuation. The dose increase to 0.2 mg twice daily also further improved urgency, micturitionand nocturia with OAB and furthermore Quality of Life(QOL), soon after the doseincrease, and the effects were maintained until week 64 or discontinuation, one year after thedose increase. Dry mouth and constipation were among the most frequent adverse eventsrelated to study medication. Dry mouth and constipation were reported by 26.5% and 9.9%of patients in the 0.1 mg twice daily arm and by 53.3% and 18.7% of patients in the 0.2 mgtwice daily arm, respectively. The majority of these events were mild in severity. There wasno clinically significant adverse effect with long−term treatment of imidafenacin 0.2 mg twicedaily. It is considered that in addition to imidafenacin standard dose(0.1 mg twice daily), adose increase to 0.2 mg twice daily, if the effect is insufficient, could provide an effective andsafe therapeutic opportunity to more OAB patients including patients who are not satisfiedwith the effect of the imidafenacin standard dose.(Jpn Pharmacol Ther 2009;37:909−30)KEY WORDS Imidafenacin, Overactive bladder, Efficacy, Safety, Long−term dose increasestudy, Quality of life(QOL)
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薬理と治療 37巻11号, 931-938 (2009);
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Background Radiotherapy and concomitant daily temozolomide chemotherapy(Rad+TMZ)in patients with primary high−grade glioma is approved under the Ministry of Health, Labourand Welfare of Japan by means of bridging study through data pooling of non−Japanese smallstudies with comparative subjects. There are few reports on the adverse events of Rad+TMZ under from clinical practice in the Japanese population.Objectives We conducted a retrospective study to evaluate the clinical safety of Rad+TMZprescribed for the treatment of primary high−grade glioma.Methods We evaluated 36 patients with primary high−grade glioma given temozolomide(75mg/m2/d)for 6 weeks concomitant with fractionated radiotherapy(60 Gy total dose:2 Gy×5 d/wk for 6 weeks). Patient records collected over a period of 70 days(maximum 77 days)from the first day of the treatment were summarized and analyzed based on the frequencyand severity of hematological toxicities, nonhematological toxicities, gender, age and dosage.Results Grade 3 hematological toxicities included lymphopenia(41.7%), severity of leukocytopenia(11.1%), and neutropenia(8.3%). Multi−way layout analysis of variance revealedthat lymphopenia was significantly increased in female and younger patients(<60 yrs). Commonnonhematological toxicities included constipation(91.7%), anorexia(77.8%), nausea(47.2%), vomiting(11.1%), headache(36.1%), and fatigue(19.4%).Conclusion From our retrospective analysis, higher frequency of adverse events of Rad+TMZ were observed compared to event rates from a short−term phaseII trial with temozolomideadministered as single therapy on anaplastic astorocytoma at first relapse. A low inci-dence of serious adverse events without requiring treatment cessation were observed in thisstudy(2.8%). Our analysis supports the tolerability of Rad+TMZ in Japanese patients withprimary high−grade glioma, with an acceptable overall toxicity profile.(Jpn Pharmacol Ther 2009;37:931−8)KEY WORDS Temozolomide, Adverse events, Primary high−grade glioma
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薬理と治療 37巻11号, 941-951 (2009);
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Background Monteplase(Cleactor_), a recombinant tissue plasminogen activator has beenused for the treatment of acute myocardial infarction. Recently, monteplase was authorized asa thrombolytic agent of acute pulmonary thromboembolism(APTE). The pharmacokinetics(PK)of low dose monteplase was examined in healthy subjects, but not in patients withAPTE at approved doses.Objectives We investigated PK and pharmacodynamics(PD)of intravenous administrationof monteplase in patients with APTE at the approved dose(13750〜27500 IU/kg). Methods Five patients were enrolled at 2 institutions from May 2007 to April 2008. In all cases, we measured plasma antigen levels and activity levels for PK assessments and coagu- lating and fibrinolytic parameters for PD. Results According to plasma monteplase antigen levels and activity levels by model inde- pendent analysis, t1/2 was 1.23-7.00 hr and 33.0-40.2 min, respectively, and CLtot was 0.46- 0.94 mL/min/kg and 1.40-2.60 mL/min/kg, respectively. These results were similar to those of compartment model analysis. By the compartment model analysis, the PK parameters including tl/2 and CL were similar between APTE patients and healthy subjects. The changes in coagulating and fibrinolytic parameters post-dose were also similar in both groups. The changes in coagulating and fibrinolytic parameters were correlated with the change in antigen and activity levels in plasma. Conclusions The PK of intravenous administration of monteplase between APTE patients and healthy subjects was not noticeably different. The PD was also correlated with the changes in monteplase antigen and activity level. It was suggested that the changes in above parameters well corresponded to pharmacological actions of monteplase in patients with APTE.(Jpn Pharmacol Ther 2009;37:941-51) KEY WORDS Monteplase, Tissue-plasminogen activator, Pharmacokinetics, Pharmacody- namics, Acute pulmonary thromboembolism
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薬理と治療 37巻11号, 953-961 (2009);
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Background In recent years, hyaluronic acid has been developed that can be edible, andingested orally as a dietary supplement that has been reported to the effect of knee pain andother degenerative knee joint disease. However, reports on the safety of oral intake is notneed to consider.Objectives A placebo−controlled, double−blind study was performed to assess the safety ofexcessive intake of tablets containing hyaluronic acid in normal healthy adults.Methods They were divided into three groups:placebo group(age 37.5±15.4 y.o.), highdosegroup(intake of 24 tablets/day, age 37.8±13.6 y.o.)and standard−dose group(intake of8 tablets/day, age 37.6±11.2 y.o.). They were given for 4 weeks. We examined at blood pressuremeasurement, physical examinations, blood test, urinalysis and interview before the trial,then 2 and 4 weeks after the start of the trial, and 2 weeks after 4 weeks intakes.Results Blood pressure, body composition, hematologic and biochemical tests in the blood,which showed some minor variations, was the change in the threshold.Conclusions The results demonstrated the safety of excess−intake of tablets containinghyaluronic acid because there were no changes to clinical problems in each test.(Jpn Pharmacol Ther 2009;37:953−61)KEY WORDS Tablets containing hyaluronic acid, Excess−intake, Safety