Volume 40,
Issue 10,
2012
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扉・目次
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Source:
薬理と治療 40巻10号, 827-828 (2012);
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REVIEW
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Source:
薬理と治療 40巻10号, 831-840 (2012);
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Compassionate use(CU) is a government program allowing the public to access unapproved drugs exceptionally to treat patients with life-threatening or seriously disabling diseases. It requires enough balance within three elements: accessibility for patients, safety insurance, and prevention of any barrier to complete clinical trials. Although the Ministry of Health, Labor and Welfare(MHLW)Advisory Committee recommended introducing CU in 2007, Japan still have not set up any program for CU. There has been a lot of discussion, but CU is still not available for the public. The crucial points of debate could be blurred by discussing at the same time on traditional quasi-CU and on the new preceding movement of using unapproved drugs. In this paper, we systematically reviewed the published literature and materials and arranged them based on what is and what is not CU. As the results, the following are considered not CU: 1) access to an off-label use of approved drugs; 2) an expanded access program(EAP) which allows a company to have early access to their promising drugs after their own judgment; 3) emergency use of unapproved drugs in a social crisis; 4) use of unapproved drugs in advanced medical care. Concerning systems relating to CU, we discussed on ‘Treatment IND’ and the ‘rule of rescue’. We also described a trend of CU in the world in 2012, e.g. the consultation on an introduction of ‘an early access to medicines scheme’ in the UK, and tightening CU by the French government regulatory reform after Mediator scandal. We then discussed what Japanese version CU is expected to be from this review. We think the following are important: 1) not to emphasize a patient’s self-responsibility too much; 2) to deal with adverse events appropriately; 3) to consider patient’s paying ability. Learning from the appropriate concept of CU and overseas experience, these problems are likely to be solved. We hope that this paper will contribute to establish a Japanese version of CU.
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CASE REPORT
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Source:
薬理と治療 40巻10号, 843-846 (2012);
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A 64-year-old man had thalamic hemorrhage on the right side since the age of 50. In addition to left hemiparesis, he had been experiencing sharp excruciating pain in the left side of his body, including his face. The pain was refractory to various analgesics. Although he had undergone motor cortex stimulation therapy at the age of 53, his pain was poorly controlled. Therefore, he was concomitantly administered anticonvulsant and antipsychotic drugs. However, because the pain was refractory to the drugs, he experienced severe anxiety, depression, and mental restlessness. Therefore, concomitant pregabalin was initiated at a low dose, and the dose was gradually increased. Eventually, his pain relieved, mental state stabilized, and nocturnal sleep improved, and he made positive efforts towards rehabilitation. Simultaneous pregabalin administration may be useful for treating central pain as well as diabetic neuropathic pain and postherpetic neuralgia when other therapeutic methods are unsuccessful.
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ORIGINAL ARTICLES
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Source:
薬理と治療 40巻10号, 847-858 (2012);
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Background Anagliptin is a novel dipeptidyl peptidase-4(DPP-4)inhibitor, whose efficacy and safety have been evaluated in nonclinical studies. In this study, we investigated the pharmacokinetic and pharmacodynamic properties of single and multiple doses of anagliptin in healthy volunteers. Methods Single dose(10-400 mg)or 7-day doses(200 mg twice a day)of anagliptin were administered orally to healthy Japanese volunteers. Pharmacokinetic and pharmacodynamic parameters were measured and investigated. Additionally, the influence of meal on the pharmacokinetics of anagliptin was determined using the 2-period crossover design. Results Administration of a single dose of anagliptin 10 to 400 mg under fasting condition showed a maximum concentration(Cmax)of 58 to 3330 ng/mL and area under the curve (AUC)0- ∞ of 202 to 12600 ng・h/mL, which increased in a dose-dependent manner. The concentration of the major inactive metabolite of anagliptin, SKL-12320, also increased in a dose-dependent manner of anagliptin. The total amount of anagliptin and SKL-12320 excreted into the urine was 55.4 to 69.6%. Anagliptin inhibited plasma DPP-4 activity in a dose-dependent manner and increased the plasma concentration of active glucagon-like peptide-1(GLP-1). Administration of multiple doses of anagliptin showed similar trends of pharmacokinetic and pharmacodynamic profiles as a single dose administration. Meal had no appreciable effect on the pharmacokinetic profile of anagliptin. We did not observe any clinically important adverse events. Conclusions The current pharmacokinetic and pharmacodynamic studies demonstrated favorable efficacy and safety profiles of anagliptin. These results indicate that anagliptin is expected to be an effective drug for diabetes.
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Source:
薬理と治療 40巻10号, 859-869 (2012);
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Background Anagliptin, a novel dipeptidyl peptidase-4(DPP-4)inhibitor, has shown good pharmacokinetic profiles in healthy volunteers. In this study, we investigated the pharmacodynamic properties of anagliptin in patients with type 2 diabetes mellitus. Methods Twenty subjects were treated with 100 mg of anagliptin twice a day or with 50 mg of sitagliptin once a day for 3 days in an open-label, 2-period crossover design. We determined the blood glucose profile over 24 h using the continuous glucose monitoring system and measured the levels of plasma glucagon-like peptide-1(GLP-1), serum insulin, serum C-peptide, and plasma glucagon. Results The 24-h area under the curve(AUC)of blood glucose, average 24-h blood glucose level, M-value, and mean amplitude of glycemic excursion(MAGE)in the anagliptin administration period were significantly lower than corresponding values in the control period. Furthermore anagliptin significantly increased the plasma level of active GLP-1 and decreased the plasma level of total GLP-1. In particular, the postprandial plasma levels of active GLP-1 were significantly higher in the anagliptin treatment period than in the sitagliptin treatment period. We did not observe any clinically important adverse events. Conclusions Anagliptin 100 mg twice a day for 3 days improved the blood glucose level over 24 h in patients with type 2 diabetes mellitus.. In addition anagliptin increased the plasma level of active GLP-1 and showed good safety profiles. These results suggest that anagliptin would be beneficial for the treatment of type 2 diabetes.
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Source:
薬理と治療 40巻10号, 871-881 (2012);
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Background Anagliptin is a novel dipeptidyl peptidase-4(DPP-4)inhibitor, and pharmacokinetic and pharmacodynamic properties of anagliptin have been investigated in healthy volunteers and in type 2 diabetes patients. In this study, we investigated the drug interaction between anagliptin and miglitol, an α-glucosidase inhibitor, in Japanese subjects with type 2 diabetes. Methods A total 18 subjects enrolled in this study received 100 mg of anagliptin twice a day and/or with 50 mg of miglitol 3 times a day for 3 days in an open-label 3-period crossover design. The pharmacokinetic and pharmacodynamic parameters were determined in each period. Results The maximum concentration(Cmax)and area under the curve(AUC)0-24h of anagliptin were decreased by concomitant administration with miglitol. The ratio of inhibition of DPP-4 activity, however, did not change markedly during 12 h on concomitant administration of miglitol. Anagliptin or miglitol alone showed a significant decrease of both fasting and postprandial glucose levels. Concomitant administration of two drugs decreased the plasma glucose levels much more significantly compared with anagliptin or miglitol alone. In addition, the postprandial levels of active glucagon-like peptide-1(GLP-1)were significantly higher in concomitant use of two drugs than in a single use of anagliptin or miglitol. We did not observe any clinically important adverse events. Conclusions Concomitant administration of anagliptin and miglitol improved the blood glucose control and increased the postprandial level of plasma active GLP-1 more effectively than either of the drugs alone. These results suggest that combination therapy with anagliptin and miglitol would be effective in the treatment of type 2 diabetes.
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Source:
薬理と治療 40巻10号, 883-894 (2012);
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Background Anagliptin is a novel dipeptidyl peptidase-4(DPP-4)inhibitor, and the pharmacokinetic and pharmacodynamic properties of anagliptin have been investigated in healthy volunteers and type 2 diabetes patients. In this study, we investigated the drug interaction between anagliptin and metformin in type 2 diabetes patients. Methods Total 18 subjects were enrolled and treated with 100 mg of anagliptin twice a day and/or with 500 mg of metformin twice a day for 3 days in an open-label 3-period crossover design. The pharmacokinetic and pharmacodynamic parameters were analyzed in each period. Results The pharmacokinetic profiles of anagliptin and metformin were not affected significantly by their concomitant administration. Furthermore, the inhibition rate of DPP-4 activity by anagliptin did not change markedly after concomitant administration with metformin. The postprandial plasma glucose levels were significantly lower in subjects treated with concomitant use of two drugs than in those treated with anagliptin or metformin alone. In addition, the postprandial levels of active glucagon-like peptide-1(GLP-1)were more significantly increased by concomitant administration than by each of these drugs alone. We did not observe any significant adverse events. Conclusions Concomitant use of anagliptin and metformin improved blood glucose control and increased the postprandial level of plasma active GLP-1 more effectively than anagliptin or metformin alone. These results suggest that combination therapy with anagliptin and metformin would be effective in patients with type 2 diabetes.
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Source:
薬理と治療 40巻10号, 897-900 (2012);
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Objectives Knee osteoarthritis is a major health problem in Japan. In the previous in vitro studies, an egg yolk peptide showed a improve effect on bone metabolism. And orally administered egg yolk peptide proved an osteoprotective effect in ovariectomized rats. The objective of this study is to verify the effect of new egg yolk peptide(iHA)to chondroprogenitor cells. Methods The in vitro effects of iHA on ATDC5 chondroprogenitor cell line were determined. The proliferation, Alcian blue staining and hyaluronic acid production were measured. Results iHA increased ATDC5 cell proliferation and hyaluronic acid production in a dose dependent manner. Furthermore, iHA promoted differentiation of ATDC5 cells into chondrocytes. Conclusions The present study suggests the ability of iHA to improve the chondrocyte metabolism. And iHA is likely to promise alternative to therapeutic agents for the management of knee osteoarthritis.
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Source:
薬理と治療 40巻10号, 901-914 (2012);
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Objectives The objective of this study was to investigate the effect of continuous consumption of the beverage containing quercetin glucosides(enzymatically modified isoquercitrin)on body fat accumulation in obese subjects. Methods A randomized, placebo-controlled, double blind intervention trial was conducted on 120 subjects with 25≦body mass index<30 kg/m2. They were divided into two groups and ingested either active beverage containing 110 mg quercetin glucosides or placebo beverage for 24 weeks. Results Abdominal total fat area, visceral fat area, and subcutaneous fat area by computed tomography reduced significantly in active beverage group compared to placebo beverage group. No adverse events related to test beverages were observed. Conclusions These results suggest that continuous consumption of the beverage containing quercetin glucosides reduced body fat safely, and might be useful for prevention and improvement of obesity and metabolic syndrome.
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Source:
薬理と治療 40巻10号, 915-919 (2012);
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Objectives We evaluated the effect of Kori-tofu on postprandial serum triglyceride, and we demonstrated the mechanism of the phenomenon. Methods Twelve healthy subjects ingested the test food(containing Kori-tofu)or control food(without Kori-tofu)alternately. Their postprandial serum triglyceride was measured. Lipid adsorption capacity of the undigested fraction of Kori-tofu and chitosan(positive control)was estimated in vitro. Results Intake of the test food significantly suppressed the elevation of postprandial serum triglyceride. Lipid adsorption capacity of the undigested fraction of Kori-tofu was comparable with that of chitosan. Conclusions Kori-tofu has the lipid adsorption effect in the intestine. As a result intake of Kori-tofu brings in the suppression of the elevation of postprandial serum triglyceride.