薬理と治療

An increase in the prescription of generic drugs(GEs)may help to reduce drug expenditure. The Japanese government has promoted the use of GEs and has proposed to expand GE sharing. However, GE sharing is still low. From 2011 to 2012, GE sharing accounted for 23.3% of the total drug volume. Since the number of brand name drugs that may be substituted by GEs has not yet been determined, we calculated the total number of drugs, original drugs, and GEs available in Japan. We searched in three Japanese databases, the master list of medicines by the Various information of Medical Fee(as released on 17 April 2012), the drugs listed on the National Health Insurance Drug Price Standard list by the Ministry of Health, Labour and Welfare(as of 17 April 2012), and the HOT Reference Numbers(as released on 27 April 2012)by the Medical Information System Development Center, and determined that the total number of drugs available in Japan as of 27 April 2012, was 17,904. Of the 17,904 drugs found, 786 drugs had an unlisted price. Moreover, 3464 of these drugs were brand name drugs, of which 2711 drugs had expired patents and/or had completed the re-examination period, and 1234 drugs could be substituted by 4098 GEs. This is the first study to determine the exact number of brand name drugs that can be substituted by GEs in Japan, which may be used as a foundation for the development of more rational drug policies and target settings.

Solid dispersion systems of probucol-polyvinylpyrrolidone showed excellent dissolution characteristics and increased bioavailability in normal rabbits. We studied the effect of solid dispersion systems on serum lipid levels to evaluate whether the amount of probucol required might be lesser than that in dosage forms currently available. A solid dispersion system of probucol-polyvinylpyrrolidone(PVP K30)(1:9 weight ratio)were orally administered to myocardial infarction-prone Watanabe heritable hyperlipidemic (WHHLMI)rabbits for 5 weeks. Serum levels of total cholesterol(T-Cho), triglycerides(TG)and phospholipids(PL)are higher in WHHLMI rabbits than in normal rabbits. Following the administration of solid dispersion systems containing 25 mg of probucol, trough plasma concentrations of probucol were significantly higher for up to 5 weeks than those containing 5 mg of probucol. Significant decreases in T-Cho, PL, high-density lipoprotein cholesterol and low-density lipoprotein cholesterol were observed following administration of solid dispersion systems containing 25 and 5 mg of probucol. Dose of 5 mg of probucol in rabbits was almost one fifth of the dose of probucol of commercial fine granules in humans by dose per weight.

Objectives Acotiamide hydrochloride hydrate(acotiamide)that enhances the gastrointestinal motility by inhibiting acetylcholinesterase activity is a new drug for the treatment of functional dyspepsia. We examined the influence of acotiamide on the antisecretory effect of acid suppressants (lansoprazole, famotidine and nizatidine) in histamine-induced gastric acid secretion. Methods A rat gastric fistula model was used for the measurement of gastric acid secretion. The gastric fistula was inserted into the forestomach and the rat was then placed in a Ballman cage. Histamine hydrochloride(8 mg/kg/h)was infused continuously through the tail vein and then the gastric juice dripped through the fistula was collected at 1 hour intervals. Lansoprazole(3 mg/kg, a proton pump inhibitor, PPI), famotidine(10 mg/kg, H2-blocker)or nizatidine(100 mg/kg, H2-blocker)was administered intraduodenally, and acotiamide(1, 10, and 100 mg/kg)was administered subcutaneously. Each sample of gastric juice up to 4 hours after administration of these drugs was titrated using an automatic titrator to the endpoint of pH 7.0. Total acid output was calculated from the gastric juice volume and acidity. Results Lansoprazole, famotidine, and nizatidine suppressed histamine-induced gastric acid secretion. Acotiamide at 100 mg/kg or lower had no influence on the antisecretory effect of these acid suppressants. Conclusions These results indicated that acotiamide does not influence the antisecretory effect of acid suppressants.

Bachground Although many studies on the pioglitazone and bladder cancer have been published in recent years, the findings seemed to be inconsistent among the studies. Most studies have been arisen from Western countries except a single Japanese study. Objective We tried to investigate the association between the use of pioglitazone and bladder cancer since it is still controversial. Methods A nested case-control study was executed using the Toyama University Hospital Database between 2005 and 2011. Cases were defined as pathologically diagnosed bladder cancer and retrieved from patients with type 2 diabetes mellitus. Controls were selected by matching with gender, age within 6 years, and visit date within 60 days. Conditional logistic regression provided an adjusted odds ratio of pioglitazone to incident bladder cancer for age, hemoglobin A1c(HbA1c), and other antidiabetic medications. Results We identified a total of 58 patients with bladder cancer. Since some patients contained missing data in the index date of incident bladder cancer and/or did not match with any controls, there were 95 patients in matched analysis. Mean age was 69 years and 26% were women. Mean HbA1c value was 7.0%. Antidiabetic drug utilization was 6% for pioglitazone, 46% for sulfonylureas, 27% for alpha-glucosidase inhibitors, and 38% for insulin. Use of pioglitazone was not associated with the risk of bladder cancer(adjusted odds ratio 0.90 [95% CI 0.09-8.89];P=0.93). Insulin, sulfonylureas, alpha-glucosidase inhibitors revealed an adjusted odds ratio 1.41, 1.16, and 0.70, respectively. Conclusion Our finding has suggested that pioglitazone might not increase the risk of bladder cancer.

Background In elderly people, Swallowing reflex is reduced with age, and aspiration is caused in many cases. Swallowing reflex is controlled by SP is synthesized in the sensory ganglia of the pharynx. By activating Transient Receptor Potential Vanilloid(TRPV), it has been reported to promote the synthesis and secretion of SP. In this study, we performed the clinical study in order to assess the effect of the functional ingredient of capsaicin that is one of the TRPV1 agonists in enhanced swallowing function for an index in saliva SP. Methods After obtaining approval from the Ethical Review Board of Kochi Medical School, a clinical study of the capsaicin film was performed to evaluate the association between each functional ingredient and its swallowing function increasing effect by saliva SP amount and sensory tests after oral ingestion. Results In the sensory tests, capsaicin film had acridity significantly compared with the placebo. The saliva SP amount in the placebo group increased temporarily due to swallowing stimulation after oral ingestion of the placebo film, but 30 minutes after the oral ingestion. capsaicin film provided an increase in the amount of saliva SP immediately after oral ingestion of the film, and showed a significantly higher value of saliva SP between 15 and 30 minutes after oral ingestion, as compared with that in the placebo group. Conclusion It was suggested that capsaicin film was likely to increase the amount of SP in saliva after oral ingestion and enhance swallowing function.

Objective The objective of this study is to assess the usefulness, safety, and user-friendliness of tocilizumab(TCZ)formulation with an autoinjector(AI)(TCZ AI)and to compare with those of TCZ pre-filled syringe formulation(TCZ PFS)in Japanese patients with rheumatoid arthritis(RA). Methods Fifty one patients with RA were subcutaneously administered TCZ at a dose of 162 mg every 2 weeks and examined the efficacy and safety of TCZ. Fifty patients who had been administered TCZ PFS by self-injection switched to self-injecting TCZ AI at Week 12 and 1 patient used TCZ AI without self-injection of PFS. The satisfaction and user-friendliness of the two injection types were surveyed in those patients and related healthcare professionals by using respective questionnaires. Results There were not observed any differences in the efficacy(ACR20, ACR50 and ACR70, DAS28-ESR)and safety(Adverse Event and Injection Site Reaction)between TCZ PFS and TCZ AI formulations. Patients with RA preferred TCZ AI formulation to TCZ PFS formulation in any questions for the satisfaction and user-friendliness in the questionnaires. The healthcare professionals answered that the user-friendliness and satisfaction of TCZ AI were better than or almost equal to those of TCZ PFS. Conclusion Present study demonstrates that TCZ AI formulation rather than TCZ PFS would be preferred by both patients with RA and health-care professionals with high satisfaction in usability, and suggests that TCZ AI formulation would be a useful option in the treatment of RA.

Objectives In this study, we investigated the effects of pitavastatin on lipid profiles and endothelial function in patients with type 2 diabetes mellitus. Methods The 63 outpatients whose low-density lipoprotein cholesterol(LDL-C)levels were over 120 mg/dL received pitavastatin(2 mg/day)for 12-16 weeks. We assessed their serum lipid levels and flow-mediated dilation(FMD)before and after treatment. Results 1)Pitavastatin treatment significantly reduced plasma LDL-C level(154±25→95±23 mg/dL, P<0.001)and plasma non-high-density lipoprotein cholesterol(non-HDLC)level(174±26→121±26 mg/dL, P<0.001). The rate of achievement of LDL-C level less than 120 mg/dL and 100 mg/dL was 89% and 68%, respectively. 2)The FMD level tended to increase(5.5±2.7→5.9±2.4%). A significant increase of the FMD level was observed in the low FMD group(FMD<5.0%)at baseline(3.1±0.8→5.2±2.1%, P<0.001). Conclusions Pitavastatin improved lipid profiles in patients with type 2 diabetes mellitus, and ameliorated endothelial function, especially in patients with low FMD levels at baseline.

A placebo-controlled, double-blind study on 30 healthy subjects(15 males and 15 females, 44±14 years old)was conducted to evaluate the safety of excessive intake of a tablet containing Bacillus subtilis C-3102 spores. Subjects were randomly divided into three groups. Each group ingested a test tablet containing either C-3102 spores at a daily dose of 5.0×109 cells or 1.5×1010 cells or the placebo tablet, without C-3102 spores, for 4 consecutive weeks. No abnormal changes were observed during the physical examination, blood analysis and urinalysis after 2 and 4 weeks of intake in the test groups. There were no clinical problems in defecation frequency in the test groups during the intake period. The number of days with defecation and digestive symptoms was not significantly different between placebo and test groups after 4 weeks of intake. No adverse events attributed to the test tablets were found in this study. Thus, these results demonstrated that a tablet containing C-3102 spores(up to 1.5×1010CFU/day)was safe for human consumption when taken daily for 4 consecutive weeks by healthy subjects.

Hyaluronic acid is one of the important skin components and plays a role of keeping good skin conditions. Because of its unique capability to bind water, hyaluronic acid has been recognized as cosmetics, and been commercially available as functional foods in recent years. In this study, we examined the effect of orally administrated hyaluronic acid on the skin condition by using photoaged model in hairless mice, which were made by long and chronic UV irradiation. Long-term UV irradiation decreased the moisture content and the amount of collagen, and decomposed hyaluronic acid into low molecular weight in the skin of photoaged model mice. Orally administrated hyaluronic acid significantly recovered the moisture content, increased the amount of collagen, and normalized depolymerization of hyaluronic acid in skin. These results suggest that orally administrated hyaluronic acid improved the UV-damaged skin.

Goishi tea is a Japanese traditional post-fermented tea that is only manufactured in Otoyo town, Kochi prefecture by a unique method. A previous study has reported the in vitro inhibitory effects of Goishi tea against H1N1 and H3N2 influenza infections. The present study was aimed to evaluate its clinical protective efficacy for children against the virus during the H1N1 2009 influenza pandemic and seasonal influenza in 2010 and 2011. Students at Otoyocho Junior High School were given Goishi tea during each outbreaks. The result of the clinical test for three years showed that the infection risk doubled, when there was no-intake of Goishi tea(odds ratio 2.0, 95%confidential interval 1.1-3.8, P=0.02). This finding indicated that Goishi tea is likely to prevent influenza infection by delaying the infection in humans.