Volume 43,
Issue 11,
2015
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扉・目次
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Source:
薬理と治療 43巻11号, 1517-1518 (2015);
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INFORMATION
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Source:
薬理と治療 43巻11号, 1521-1522 (2015);
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REVIEW
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Source:
薬理と治療 43巻11号, 1529-1532 (2015);
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ORIGINAL ARTICLES
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Source:
薬理と治療 43巻11号, 1535-1541 (2015);
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Objectives When pharmacists prepare medications for dialysis patients, they often have the impression that the patients receive too many medicines, or what they call“Heavy Prescriptions.” We investigated the prescriptions for dialysis patients and what pharmacists think about them. Methods 1.We examined 332 periodical prescriptions in four maintenance hemodialysis facilities. We classified the prescribed medicines based on pharmacotherapeutic class and summed them up in each class. 2.Twenty pharmacists filled out a questionnaire to express their views on prescriptions for dialysis patients. Results1.On average, 9.42 medicines were prescribed per person. Overall, 3128 medicines were prescribed: 22.4% were antihypertensives, 19.2% were specific agents for dialysis (including phosphate binders, potassium binders, cinacalcet, and nalfurafine), 9.1% were anti-gastric ulcer agents, and 8.1% were anti-thrombotic agents. In four facilities almost the same medicines were prescribed, and in almost the same manner. 2.Seventy-percent of the pharmacists answered that too many medicines were prescribed. Sixty-percent answered that medications could be reduced. ConclusionsThe prescription records showed that dialysis patients received 9.42 medicines per person. This was consistent with the pharmacistsʼ belief that dialysis patients receive too many medicines. Decreased medication of dialysis patients would prevent side effects caused by drug accumulation and drug interactions. It also could be potentially useful for reforming the medical economy. Pharmacists should participate in the planning of medication regimens for dialysis patients.
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Source:
薬理と治療 43巻11号, 1543-1551 (2015);
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Objectives Flutiform(R) is a combination drug of fluticasone propionate(FP)and the formoterol fumarate dihydrate(FOR), but there are few reports that examined combined effect by this combination. Therefore, in this study, we examined inhibitory action by FOR, FP alone and the combination for the antigen-induced contraction of respiratory tract using a rat asthmatic model. Methods The Wistar rats were given ovalbumin plus alum subcutaneously and sensitized it. We gave an antigen intravenously 10-21 days later and caused contraction of respiratory tract. FOR and salmeterol xinafoate(SAL)were administered 15 minutes before antigen stimulation, and FP and budesonide(BUD)were administered 4 hours before antigen stimulation by intratracheal aerosol. After having immobilized a rat under anesthesia, we measured airway pressure under mechanical ventilation. Results FOR and SAL significantly inhibited a change of the respiratory tract inspiratory pressure in more than 0.3 and 3μg╱kg after the antigen administration, respectively. Nevertheless FP and BUD did not inhibit respiratory tract inspiratory pressure. FOR 1μg╱kg and FP 10 μg╱kg or FOR 0.1μg╱kg and FP 10μg╱kg combination administrated group significantly inhibited the contraction of respiratory tract more than each FOR-alone group. The combination of BUD and FOR or SAL and FP was not found in the statistical significant difference as compared with each β2 agonist alone group. Conclusions For contraction of respiratory tract induced by the antigen stimulation in sensitized rat, combination treatment of FOR and FP attenuated inhibition of contraction of respiratory tract more than FOR alone.
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Source:
薬理と治療 43巻11号, 1553-1560 (2015);
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Background Monthly oral ibandronate 100 mg tablet has been developed for the treatment of osteoporosis in Japan. To investigate the pharmacological difference with a fasting interval of 30 minutes(min)compared to a fasting interval of 60 min, clinical pharmacology studies were performed. Methods This report summarizes the results of two single-center clinical pharmacology studies.One is to investigate the bioavailability of 2.5 mg ibandronate tablet taken 60 min before a meal compared to 2.5 mg ibandronate tablet taken 30 min before a meal, and 5 mg ibandronate tablet taken 30 min before a meal in healthy postmenopausal females. Second is to investigate bioavailability of 50 mg ibandronate tablet taken 60 min before a standard meal compared to 50 mg ibandronate tablet taken 30 min before a standard meal in both healthy males and healthy postmenopausal females. Results AUClast at fasting interval of 60 min after oral administration of 2.5 mg ibandronate was 1.40±0.77 4 ng・h╱mL (Mean±SD)(n=24), that at fasting interval of 30 min after oral administration of 2.5 mg ibandronate was 1.12±0.950 ng・h╱mL(n=24), and that at fasting interval of 30 min after oral administration of 5 mg ibandronate was 1.96±1.11 ng・h╱mL(n=24). AUClast at fasting interval of 60 min after oral administration of 50 mg ibandronate was 16.0±15.6 ng・h╱mL(n=24), that at fasting interval of 30 min after oral administration of 50 mg ibandronate was 11.1±23.5 ng・h╱mL(n=24). Conclusions The relative bioavailability after a single oral dose of 2.5 mg and 50 mg ibandronate as measured by AUClast was lower when the fasting period was shortened from 60 min to 30 min prior to a standard meal. Accordingly, ibandronate should be taken after getting out of bed, before the first food or drink of the day, and food or drink other than water should be avoided for at least 60 minutes after taking ibandronate.
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薬理と治療 43巻11号, 1561-1574 (2015);
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Background Kyushin is an over the counter drug for amelioration of a palpitation, short of breath and as a restorative. We reformulated some ingredients in Kyushin for protection of endangered animals which are used as an ingredient source, and for matching an aged society in Japan. Objectives The aim of this study was to investigate an efficacy and safety of the new prescription of Kyushin. Methods A randomized double-blind parallel-group study was conducted with volunteers who have some indefinite complaints related to cardiovascular medicines. Subjects(40 subjects: aged 32 to 75)were randomly allocated to 2 groups. Subjects in each group(male╱female=10╱10)were orally received 6 pills of Kyushin(new or former prescription)daily for 4 weeks, and recorded a score of complaints, in addition, the POMS test, an autonomic nervous function test, and laboratory examination were conducted. Results Both groups showed the significant ameliorating effect in the score of indefinite complaints and POMS test, and the efficacy was more remarkable in the new prescription. No adverse effect was observed during this study. Conclusion This study shows that the new prescription of Kyushin is not only safe, but it is more effective on the indefinite complaints related insufficient blood circulation, autonomic nerve dysregulation and mood malaise than the former one.
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薬理と治療 43巻11号, 1577-1583 (2015);
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Objectives Hypertriglyceridemia contributes to diabetic nephropathy. In UKPDS 74, hypertriglyceridemia was detected as one of the risk factors for diabetic nephropathy. Increased remnant lipoproteins underlie hypertriglyceridemia. We first found that apolipoprotein(apo)E2 is a genetic factor for diabetic nephropathy, and that increase of plasma TG╱remnant lipoproteins caused by apo E2 contributes to diabetic nephropathy. Remnant lipoproteins are taken up by mesangial cells, and then cause renal damage. The frequency of apo E2 is approx. 10% in Japan and western countries. Diabetic nephropathy is characterized by the accumulation of extracellular matrix protein(type Ⅳ collagen)in the glomerular mesangium. TGF-β stimulates typeⅣ collagen protein synthesis. Incretin-related drugs, which are widely used in diabetic patients, reduce plasma TG╱remnant lipoproteins as well as plasma glucose. There is little information about the effect of incretin on diabetic nephropathy. In the present study we examined whether sitagliptin, DPP-4 inhibitor, which acts through increasing incretin is effective to improve nephropathy in type 2 diabetic patients with apo E2 allele, and examined the effects of GLP-1 on TGF-β and type Ⅳ collagen expression in human mesangial cells(HMCs)loaded with apo E2 remnant lipoproteins. Methods Type 2 diabetic patients with apo E3╱3 genotype(n=38)and apo E3╱2 genotype (n=7)were studied. Patients were treated with sitagliptin(50 mg╱day)over 10 months. HbA1c, plasma TG and remnant cholesterol were compared before and after sitagliptin therapy. Remnant cholesterol was determined as RLP︱cholesterol(normal range<5.2 mg╱dL). Urinary albumin-to-creatinine ratio(ACR, normal range<30 mg╱g cre)was measured as a marker of nephropathy. Remnant lipoproteins were isolated from plasma of a patient with type 2 diabetes and apo E2╱2 genotype by ultracentrifugal method. HMCs loaded with remnant lipoproteins were incubated for 24 h with GLP-1 at the concentration of 0, 100, 300 and 500 nmol╱L. To evaluate the expression of TGF-β, type Ⅳ collagen and GLP-1 receptor m-RNA in HMCs, PCR procedure was performed. Results In apo E3╱3 patients, 10-month therapy with sitagliptin significantly reduced HbA1c (6.6→6.0%, P<.001), plasma TG(129→107 mg╱dL, P<0.05)and remnant cholesterol (5.5→3.9 mg╱dL, P<0.001), and ACR(57.4→34.1 mg╱g cre, P<0.05). In apo E3╱2 patients, it reduced HbA1c(6.8→6.0%, P<0.001), plasma TG(173→119 mg╱dL, P<0.05)and remnant cholesterol(8.0→5.0 mg╱dL, P<0.001), and ACR(119.0→19.2 mg╱g cre, P<0.001). Reduction in HbA1c from baseline at 10 months was not significantly different between apo E3╱3 patients and apo E3╱2 patients, but reduction in plasma TG and remnant cholesterol, and ACR from baseline at 10 months was significantly(P<0.05)greater in apo E3╱2 patients than in apo E3╱3 patients. The next study using renal mesangium cells was conducted to elucidate the mechanism by which sitagliptin reduces ACR. Apo E2 remnant lipoproteins significantly(P<0.001)stimulated the expression of TGF-β and type Ⅳ collagen mRNA in HMCs. Exendin-4 which is an incretin mimic and has activity similar to GLP-1 significantly(P<0.001)suppressed the expression of TGF-β and type Ⅳ collagen mRNA in HMCs loaded with apo E2 remnant lipoproteins in a dose-dependent manner. Exendin︱4 significantly(P<0.001)stimulated the expression of GLP-1 receptor. Conclusions Sitagliptin reduced plasma TG╱remnant lipoproteins, and ACR more greatly in apo E2 diabetic patients. GLP-1 suppressed the expression of TGF-β and type Ⅳ collagen in HMCs loaded with apo E2 remnant lipoproteins. It is suggested that incretin is effective to protect and improve diabetic nephropathy associated with apo E2 through its lowering effect of plasma TG╱remnant lipoproteins and╱or its direct effect on renal mesangial cells.
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Source:
薬理と治療 43巻11号, 1585-1592 (2015);
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Objectives To compare the efficacies of extended-release exenatide (BYDUREON(R) 2 mg for subcutaneous injection; EQW)and insulin glargine(Ins), and identify predictors╱predicting factors of the HbA1c-lowering effects of EQW in Japanese and Asian patients with type 2 diabetes. Methods HbA1c data from two phase III trials were analyzed: GWBX(26 weeks: EQW versus Ins)and GWCK (26 weeks: EQW versus twice︱daily exenatide). Body weight at 26 weeks of GWBX were also assessed. Changes of HbA1c and weight at 26 week in GWBX categorized into 4 groups were evaluated. HbA1c change was stratified by patient characteristics (BMI, diabetes duration, sulfonylurea use)and analyzed. Change in HbA1c at 26 weeks in EQW-treated patients in GWCK were also compared between patients with and without injection site nodules. Results Regardless EQW and Ins, approximately 80% of all patients in GWBX experienced reductions in HbA1c. However, weight gain occurred╱observed in 30% in EQW arm compared to 55% in Ins arm. EQW patients with a BMI<20 kg╱m2 at baseline and EQW patients with shorter disease duration experienced the greatest reduction. GWBX patients with previous Sulfonylurea use showed the tendency of attenuated HbA1c reduction. Injection site nodules were not associated with the HbA1c change in EQW-treated patients in GWCK. Conclusion These analyses confirmed the effects of EQW on glycemic control and body weight in Japanese and Asian patients with type 2 diabetes. The HbA1c-lowering effect of EQW was not associated with BMI at baseline and disease duration; however, patients with shorter disease duration and patients never used sulfonylurea indicated greater HbA1c reduction in these studies. The HbA1c-lowering effects of EQW was not associated with the injection site nodules. From aforementioned reasons, EQW demonstrated effects in diverse patients and usefulness in early intervention.
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Source:
薬理と治療 43巻11号, 1593-1600 (2015);
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Objectives To evaluate the efficacy of glucosylceramide extracted from pineapple for the skin, a randomized, double-blind, placebo-controlled, parallel-group trial was conducted on healthy volunteers who are concerned about dullness and dryness of their skin. Methods Seventy adult subjects(Japanese men and women aged 20-59 years)were randomly assigned to receive either a tablet containing 1.2 mg of glucosylceramide extracted from pineapple or a placebo once daily for 12 weeks. The primary endpoints included transepidermal water loss(TEWL), skin moisture content, color difference(L* value, a* value, b* value), and skin texture. A safety assessment as a secondary endpoint was also performed by interview with a medical doctor. Results After excluding deviants, the number of subjects analyzed was 61. In the group which took the tablet containing 1.2 mg of glucosylceramide extracted from pineapple, TEWL was significantly decreased and the L* value was significantly increased after ingestion for 12 weeks. In addition, any clinical adverse events were not found throughout the study period. Conclusion The present study suggests that daily consumption of glucosylceramide extracted from pineapple could improve barrier function and tone of the skin.
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INFORMATION
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Source:
薬理と治療 43巻11号, 1603-1609 (2015);
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Source:
薬理と治療 43巻11号, 1611-1621 (2015);
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Source:
薬理と治療 43巻11号, 1622-1625 (2015);
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