薬理と治療

We are conducting the 8-week post-marketing surveillance to evaluate safety and efficacy (evaluated by physicians and patients)of paroxetine controlled-release(paroxetine CR)in patients in depressive state/depression seen in clinical practice. For the safety analysis, adverse events were collected. The primary efficacy measure was improvement rating by physicians. The satisfaction rating with paroxetine CR therapy was assessed using satisfaction questionnaire for patients. The available information on safety and efficacy of paroxetine CR is limited now. Since it is important for implementation of appropriate use to provide information already collected through this post-marketing surveillance as soon as possible, the interim analyses were planned. The survey for 1232 cases was completed by the end of January 2013. The interim analyses were implemented for these cases. The safety analysis was performed for 1150 cases. The incidence of adverse events was 10.7%(123/1150). The major adverse events were nausea, somnolence and constipation. All adverse events were not serious and no outstanding issues were observed based on the findings of the interim analyses. The proportion of patients remaining on paroxetine CR therapy at 8 weeks was 82.0%(943/1150, 95% confidence interval, 79.7-84.2). The efficacy analysis was conducted for 1067 cases and improvement rate of this population at 8 weeks(by the last observation carried forward)was 71.1%(759/1067, 95% confidence interval, 68.3-73.8). The patient satisfaction rate was 68.2%(726/1064, 95% confidence interval, 65.3-71.0) We will continue the post-marketing surveillance to confirm safety and efficacy of paroxetine CR in patients in depressive state/depression seen in clinical practice.

ChondroHi900E has a daily dose of five active ingredients, tocopherol acetate 100 mg, red ginseng dry extract 300 mg(equivalent to 3000 mg red ginseng), sodium chondroitin sulfate 900 mg, nicotinamide 12 mg, and panthenol 20 mg, and is an over-the-counter drinkable preparation for improvement of excessive sensitivity to cold (hiesho). The usefulness of ChondroHi900E in improving hiesho was compared with that of placebo in a double-blind crossover study. Ten female patients(22-40 years old)with hiesho took ChondroHi900E or placebo in a crossover fashion. The temperature of the right hand loaded with cold water was measured by dermal thermography as an objective indicator. In addition, warmth of the body was evaluated as a subjective indicator. The results revealed that ChondroHi900E significantly improved the recovery of temperature of the right hand after cold water loading as compared to placebo. In addition, subjects reported feeling body warmth at a significantly higher frequency after the intake of ChondroHi900E than after placebo. The above results suggest that ChondroHi900E is useful for improving hiesho.

Hyaluronic acid plays an important role for water keeping in skin. Because of its unique capability to bind water, hyaluronic acid has been recognized as cosmetics, and in addition, has been commercially available as functional foods in recent years. In this study, we investigated the effect of orally administrated hyaluronic acid on the skin condition by using UV irradiated mice. UV irradiation significantly decreased the moisture content and the amount of hyaluronic acid in skin of hairless mice. Orally administrated hyaluronic acid significantly suppressed the decrease of the moisture content, and increased the amount of hyaluronic acid in skin of hairless mice. These results suggest that orally administrated hyaluronic acid alleviated the UV damaged of the skin.

Background Orally-administered L-ornithine(Orn)is metabolized by ornithine-δ-aminotransferase(OAT). In humans, a deficiency in OAT results in gyrate atrophy of the choroid and retina, an autosomal recessive trait characterized by hyperornithinemia. However it is unknown whether long-term supplementation of L-ornithine hydrochloride(ORN•HCl)affects blood Orn kinetics and retinal function. The aim of the current study was to determine the influence of orally-administered ORN•HCl on metabolic changes and clinical health status in healthy subjects. Methods In an open-label trial, 16 healthy subjects received 3.0 g/d of ORN•HCl for 3 months. Plasma Orn, clinical and biological indices were measured. Pharmacokinetic parameters including AUC06h, Cmax, Cmin, and Tmax following 1.0 g oral ORN•HCl loading, and changes in retinal function by using flash electroretinography(ERG)were also evaluated before and after the study period. Results When compared with the baseline value, slight but significant decreases in basal levels of plasma Orn were observed after ORN•HCl intake. The ORN•HCl loading test increased plasma Orn concentrations, indicating a significant reduction in Cmax after the 3-month study period compared with the baseline result. The other pharmacokinetic parameters and ERG results had not changed. None of the subjects experienced clinically relevant or any side effects. Conclusions These observations indicated that ORN•HCl supplementation increased plasma Orn levels transiently but did not cause Orn accumulation or affect retinal function in healthy people.

Objectives The aim of the present study was to investigate the effect of cooked rice with β-glucan enriched barley on postprandial glucose response and its second-meal effect. Methods The study was conducted in randomized crossover design with twenty healthy subjects whose fasting blood glucose was normal level. Subjects consumed test meals at breakfast and blood glucose, insulin and free fatty acid were measured for 120 min after the breakfast. For a subsequent lunch, they consumed standardizes meals and blood glucose was measured for 120 min after the lunch. Results Cooked rice with β-glucan enriched barley lowered the blood glucose and insulin incremental areas under the curve(IAUC)(0-120 min)at breakfast and the blood glucose IAUC(0-120 min)at a subsequent lunch(P<0.05). The blood free fatty acid was not changed after ingestion of the test meals at breakfast. Conclusions These findings suggested that cooked rice with β-glucan enriched barley contributed to postprandial glucose response and its second-meal effect. The present study suggested that cooked rice with β-glucan enriched barley has potential to an advantage for diabetes care.

Objectives Administration of L-ornithine increases ammonia detoxification by the urea cycle in the liver. Some ammonia is secreted from the skin through sweat and gas. In this study, we examined the effect of L-ornithine intake on the transdermal secretion of ammonia evoked by ergometer exercise. Methods A double-blind crossover human trial was performed with 20 healthy adult Japanese men. Subjects took glycine(as a placebo)or 2.4 g L-ornithine before attending an incremental ergometer exercise. Ammonia concentrations in blood and transdermal secretions were measured before and after exercise. Results Incremental ergometer exercise transiently increased blood ammonia concentrations and transdermal ammonia secretion. L-ornithine ingestion significantly reduced transdermal secretion of ammonia and tended to reduce blood ammonia concentrations induced by exercise. Conclusions L-ornithine intake before exercise suppressed the increase in transdermal ammonia secretion. This effect of L-ornithine is probably caused by an increase in urea cycle function in the liver.

Saxagliptin is a potent, selective DPP-4 inhibitor approved as an adjunct to diet and exercise to improve glycemic control in type 2 diabetes mellitus(T2DM)in USA on July, 2009, and thus far has been launched over 84 countries of the world. In patients with T2DM, oncedaily administration of saxagliptin before breakfast shows the sustained inhibition on plasma DPP-4 activities and then the reduction of postprandial hyperglycemia even after dinner associated with increase in plasma GLP-1 levels. The clinical development study in Japan also supported its usefulness for T2DM. Saxagliptin 2.5 and 5 mg led to the significant improvements in glycemic indices HbA1c, and were generally well tolerated in T2DM. Treatment of saxagliptin 5 mg induced the sustained reduction in HbA1c through 52 weeks. The long-term combination therapy with saxagliptin and other oral hypoglycemic agents provided sustained glycemic control and was well tolerated for up to 52 weeks. Saxagliptin as add-on to sulfonylurea or glinide has a tendency to increase hypoglycemia but not to other oral antidiabetic agents(α-glucosidase inhibitor, a metformin or a thiazolidinedione).These results of clinical trials confirmed the long-term efficacy and safety of saxagliptin monotherapy as well as add-on combination therapy, and supported its usefulness as a therapeutic agent for T2DM. Saxagliptin has less concern for hypoglycemia and weight gain which often become problems in routine care. The meta-analysis of clinical trials in USA showed there was evidence of no risk increasing cardiovascular events associated with saxagliptin, suggesting the superior of saxagliptin in safety. Thus, saxagliptin is applicable for various pathological conditions and considered to be clinically significant as a new therapeutic option for T2DM.