Search

Lipid lowering therapy using statins prevents the risk of cardiovascular events. However, since the year 2000, there have been some reports that statins increased the risk of developing diabetes (SIRDD). It is socially demanded that pharmacists must apply pharmacotherapy to patients by utilizing drug information like the above, such as selecting appropriate drugs and providing correct drug information. Accordingly, pharmacists must correct drug information, and they should analyze and evaluate such information. Therefore, we conducted a questionnaire survey for pharmacists in community pharmacies with an aim to verify relevance between methods of obtaining drug information and the utilization of the information of "SIRDD" as a subject. We sent a questionnaire by letter to 1522 pharmacists in Fukushima and Mie prefecture, and received the results of the questionnaire from them using "Google forms" that is software to make web questionnaire and letters. We obtained responses from 356 (23.4%) pharmacists out of 1522. The number of responses from the pharmacists that "know" the information of "SIRDD" was 135 (37.9%). We found that these pharmacists obtained the information by websites of pharmaceutical companies, m3, Inc. (Portal site for medical professionals), and Pharmaceuticals and Medical Devices Agency (PMDA), as the sources of information. Our results suggested that pharmacists responded that they "know" "SIRDD" utilized websites as a quick information tool. The difference in network environments will relate to the difference of providable medical quality. So, it is very important to maintain appropriate network environment in cooperation with medical institutions, professional associations and the government.

"Academic detailing" is used to clearly explain scientific issues. In the field of clinical practice, "academic detailing" is a form of interactive educational outreach to physicians in order to provide unbiased, non-commercial, evidence-based information about medications and other therapeutic modalities, with the goal of improving patient care. It is necessary to provide proper information about prescription drugs for their appropriate use in clinical practice. However, this requires of physicians significant time and labor to comprehensively collect and summarize all necessary information for the proper clinical application of pharmaceutical products, a task which may be both difficult and prohibitive to a busy physician. However, if clinical experience and other pharmaceutical or treatment information is derived solely from the commercial entities, this may lead to improper prescription practices. In western countries, public funds are used to support universities and other research institution programs. In Canada, clinical pharmacists act as "detailers". Their mission and role is to listen to the needs of the physician or health care professional, to provide objective, evidence-based drug information on selected drug therapy topics, to educate physicians on the optimal use of medications, to provide practical alternatives, and to extend the physician's usable knowledge base. The importance of this "academic detailing" activity is also recognized in Japan, and pharmacists can be expected to act as detailers in the future. We hope that this will lead to improvement in the quality of medical care.

Tacrolimus ointment is used worldwide to treat atopic dermatitis. Although tacrolimus ointment is not suitable for clinical admixtures, it is often mixed with various ointments or creams, such as corticosteroids, antibacterial agents, and moisturizing agents. There is only one report of quality testing of admixtures of tacrolimus ointment with adaparene gel (Differin® Gel). In this study, we used HPLC to evaluate the pharmaceutical stability of tacrolimus mixed with eight different dermatologic ointments or creams. No decrease in the tacrolimus content was observed in any of the mixtures after 4 weeks of storage at room temperature, indicating that tacrolimus admixtures are stable.

According to the Japanese revitalization strategy endorsed by the government in June, 2013, pharmacies are expected to play an active role as the hub of health information. But this is not sufficiently organized: an infrastructure for providing neutral information which becomes the basis of such health information is not yet established for healthcare professionals, patients and consumers. As for drug information available subsequent to the marketing of pharmaceutical products, information from the pharmaceutical companies including Package Inserts and Interview-forms are often found. However, though such information from companies is important, it is necessary for healthcare professionals and patients to have access to the information evaluated by a trustworthy third party. With overseas distribution, the dissemination of drug information is provided by third parties, which are independent of regulatory agencies. For example, National Health Service (NHS) Evidence in the UK offers wide-ranging information based on evidence from a disease to pharmaceutical products, and is a widely available information source for healthcare professionals, patients and consumers. With regard to therapeutic medications, drug information and health foods in the Japanese community, it is necessary for patients and healthcare professionals that we establish neutral and common systematic information based on the research evidence. By providing information on the Internet, which enables people to access the information easily and to assess a product's usefulness objectively, we hope to eventually develop a system that ensures a patient's safety in the use of drugs.

Patients and consumers have desired high quality drug information in their pharmacotherapy, and are entitled to receive it. It is desirable that the information should be aimed at shared decision-making between patients and healthcare professionals about medications. The quality of drug information available to patients should also be assured. With an aim to improve the quality of "Drug Guide for Patients", we investigated Patient Information Leaflets (PILs) which are approved by the Medicines and Healthcare Products Regulatory Agency (MHRA) in the United Kingdom (UK) with regard to the criteria of development and user testing for assuring the quality of the PILs. In the European Union (EU), these are called Package Leaflets (PLs). PILs have been a legal requirement in the UK since 1999 for all medications. The user testing of PILs has been implemented as evidence since 2005 so that people can rely on the information provided in the leaflet. Execution of PILs which follow the guidance of the user testing, according to the guidance of this user testing, would reflect the views of patients. Here, we introduce the development process and implementation of user testing of PILs. In terms of readability, accessibility and understandability of drug information for patients, we need to discuss involving the public in decisions on how its quality should be assured and how it can be made easily be comprehensible for patients, in order to make effective use of "Drug Guide for Patients" in the future in Japan.

Michiko Yamamoto,1 Hirohisa Doi,1 Ken Yamamoto,2 Kazuhiro Watanabe,2 Tsugumichi Sato,3 Machi Suka,4 Takeo Nakayama,5 Hiroki Sugimori6 1Department of Drug Informatics, Center for Education & Research on Clinical Pharmacy, Showa Pharmaceutical University, Tokyo, Japan; 2Department of Pharmacy Practice, Center for Education & Research on Clinical Pharmacy, Showa Pharmaceutical University, Tokyo, Japan; 3Faculty of Pharmaceutical Sciences, Tokyo University of Science, Chiba, Japan; 4Department of Public Health and Environmental Medicine, The Jikei University School of Medicine, Tokyo, Japan; 5Department of Health Informatics, Kyoto University School of Public, Kyoto, Japan; 6Department of Preventive Medicine, Graduate School of Sports and Health Sciences, Daito Bunka University, Saitama, Japan Background: The safe use of drugs relies on providing accurate drug information to patients. In Japan, patient leaflets called Drug Guide for Patients are officially available; however, their utility has never been verified. This is the first attempt to improve Drug Guide for Patients via user testing in Japan.Purpose: To test and improve communication of drug information to minimize risk for patients via user testing of the current and revised versions of Drug Guide for Patients, and to demonstrate that this method is effective for improving Drug Guide for Patients in Japan.Method: We prepared current and revised versions of the Drug Guide for Patients and performed user testing via semi-structured interviews with consumers to compare these versions for two guides for Mercazole and Strattera. We evenly divided 54 participants into two groups with similar distributions of sex, age, and literacy level to test the differing versions of the Mercazole guide. Another group of 30 participants were divided evenly to test the versions of the Strattera guide. After completing user testing, the participants evaluated both guides in terms of amount of information, readability, usefulness of information, and layout and appearance. Participants were also asked for their opinions on the leaflets.Results: Response rates were 100% for both Mercazole and Strattera. The revised versions of both Guides were superior or equal to the current versions in terms of accessibility and understandability. The revised version of the Mercazole guide showed better ratings for readability, usefulness of information, and layout (p

Lithium mesitylmethyl(trimethylsilyl)amide behaved as a nice amination agent in a chiral ligand-controlled conjugate addition reaction of tert-butyl cinnamate to give the conjugate amination product with 99% ee in 90% yield. Other acyclic and cyclic enoates were also aminated in reasonably high enantioselectivity, while the deprotonation of abstractable proton of enoates caused yield loss of the conjugate amination products, due to the bulkiness and enriched basicity of the lithium amide. Although such steric bulkiness made hard the hydrogenolytic cleavage of a mesitylmethyl–N bond of the adducts, a new protocol comprising N-chlorination–regioselective dehydrochlorination–transoximation was developed for N-dearylmethylation, giving 3-aminoalkanoates in reasonably good yields.

A simple method for the direct synthesis of 2,2′-binaphthols 2 and dinaphtho[1,2-b;2′,1′-d]furans 3 under mild conditions was developed, utilizing a biaryl coupling reaction via electron donor–acceptor complexes of 1-naphthols with SnCl4. Heating of the complex in a sealed tube for (18–24 h) afforded the corresponding o–o coupled product 2 in excellent yield. Prolonged reaction (56–65 h) under the same conditions afforded 3 in high yield in one step. We also found that in the case of α-naphthol without substituents other than a hydroxyl group at the C-1 position, regioselective o–o coupling reaction proceeded. The products 2a, 2b and 2g should be useful as synthetic intermediates for naturally occurring 3,3′-bijuglone, 3,3′-biplumbagin and elliptinone.

Michiko Yamamoto,1 Kiyoshi Kubota,2 Mitsuhiro Okazaki,3 Akira Dobashi,3 Masayuki Hashiguchi,4 Hirohisa Doi,1 Machi Suka,5 Mayumi Mochizuki4 1Education Center for Clinical Pharmacy Practice, Showa Pharmaceutical University, Tokyo, Japan; 2Department of Pharmacoepidemiology, Graduate School of Medicine, University of Tokyo, Japan; 3Education and Research Institute of Information Science, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan; 4Division for Evaluation and Analysis of Drug Information, Faculty of Pharmacy, Keio University, Tokyo, Japan; 5Department of Public Health and Environmental Medicine, The Jikei University School of Medicine, Tokyo,Japan Background: Patients have been allowed to report adverse drug reactions (ADRs) directly to the government in some countries, which would contribute to pharmacovigilance.Objective: We started a pilot study to determine whether web-based patient ADR reporting would work in Japan. This article aims to describe the characteristics of the patient reporters, and to clarify patient views and experiences of reporting.Methods: Patients who submitted online ADR reports were contacted to respond to an ADR reporting questionnaire; only consenting reporters were included. Subjects with multiple responses were excluded from analysis. The questionnaire consisted of both closed and open questions. Questionnaire responses were examined using Pearson’s chi-squared test.Results: A total of 220 web-based ADR reports were collected from January to December 2011; questionnaires were sent to 190 reporters, excluding those who gave multiple reports and those that refused to be contacted. Responses were obtained from 94 individuals (effective response rate: 49.5%). The median respondent age was 46.0 years. Sixty-three respondents found out about this pilot study on the Internet (67.0%). The numbers of respondents claiming that they had difficulty recalling the time/date of ADR occurrence were 16 patient reporters and three non-patient reporters. The number of reporters who found it difficult to complete the online reporting form was 22 patients (26.2%) and one non-patient (10%). Fifty-seven respondents (60.6%) expected feedback after reporting and many respondents wanted to know the process of ADR data collection and related information. Seventy-three respondents (77.7%) stated that they would report ADRs again in future.Conclusion: Throughout the entire questionnaire, online patient ADR reporting was received with a forward-looking, positive approach. To facilitate smoother web-based reporting experiences in future, some improvements may be required in online ADR reporting forms, particularly with regard to respondent feedback. Keywords: adverse drug reaction reporting system, patient safety, patient experience, pharmacovigilance

Systematic structure tuning of lithium amides derived from benzyl- N -TMS-, allyl- N -TBDMS-, and diisopropylamines lead to several candidates including anthracen-9-ylmethanamine which provided high performance in the enantioselective 1,4-addition (91% ee) and following hydrogenolysis with 10% Pd/C-H 2 in methanol to afford β-amino ester.

Pharmacokinetic-pharmacodynamic (PK-PD) modeling and simulation can be an invaluable tool for use in making crucial decisions in drug development and clinical settings, including those pertaining to compound selection, dose selection, study design, and patient population, all of which can impact the cost of development and treatment. Clinical PK-PD modeling and simulation of antimicrobial agents are possible because minimum inhibitory concentration (MIC) values can be easily measured in the hospital laboratory. However, no such easily measured clinical markers are available for many other types of drugs. In this point of view, we thought that the proteomics approach may be available for find the direct PD parameter such as drug specific biomarker. Many reports also suggest that proteomics is a promising tool in the search for drug-specific biomarker proteins that could be used in PK-PD modeling and simulation. Thus, by enabling examination of drug-induced changes in the expression of specific biomarker proteins, proteomic data could be used in PD analyses in much the same way that MICs are used in PD evaluations of antimicrobial agents.

A simple method for the direct synthesis of 2,2′-binaphthols was developed, utilizing aryl–aryl coupling reaction via electron donor–acceptor complexes of 1-naphthols with SnCl 4 . Heating of the complex in a sealed tube afforded the corresponding o - o coupling product in excellent yield. This method was utilized for a biomimetic synthesis of the binaphthoquinone, 3,3′-biplumbagin, isolated from Plumbago zeylanica .

We investigated the reactions of various 1-naphthols (NPOHs; 1) with p-benzoquinones (Qs), such as 1,4-benzoquinone (BQ) and p-chloranil (CA), as pi-electron acceptors. With electron-rich NPOHs 1a-c, oxidative biaryl coupling and subsequent dehydrogenation reaction took place selectively to give the corresponding 2,2'-binapthyl-1,1'-quinones 3a-c in excellent yield. In the case of electron-deficient NPOHs 1e, f, two different types of reactions occurred in the presence of SnCl4 and ZrO2 under similar conditions: SnCl4 mediated oxidative dimerization and trimerization of NPOH, while ZrO2 promoted electrophilic arylation of Qs with NPOH. The resulting products 3 would be useful synthetic intermediates for naturally occurring diosindigo B, biramentaceone and violet-quinone.

The chiral ligand controlled asymmetric conjugate addition reaction of lithium N-allyl-N-(tert-butyldimethylsilyl)amide to alkenoates proceeded smoothly to give, after protodesilylation, the corresponding 3-allylaminoalkanoates with high enantioselectivities in high yields. The allyl group on the nitrogen atom was easily removable to afford 3-aminoalkanoates.

The reaction of lithium ester enolate with enones provides a challenge for chemoselectivity, that is, discrimination between a conjugate addition and a 1,2-addition. Asymmetric conjugate addition of a lithium enolate of α-trimethylsilanylacetate to acyclic and cyclic α,β-unsaturated ketones was mediated by an external chiral ligand to give the corresponding 1,4-adducts in good enantioselectivity of 74% and good chemoselectivity.

The reaction of lithium ester enolate with enones provides a challenge for chemoselectivity, that is, discrimination between a conjugate addition and a 1,2-addition. Asymmetric conjugate addition of a lithium enolate of alpha-trimethylsilanylacetate to acyclic and cyclic alpha,beta-unsaturated ketones was mediated by an external chiral ligand to give the corresponding 1,4-adducts in good enantioselectivity of 74% and good chemoselectivity.

The external chiral ligand-controlled asymmetric conjugate addition reaction of lithium amides with α,β-unsaturated esters provided β-amino esters in high yields and high enantioselectivities.

A simple method was developed for the direct synthesis of 2,2′-binaphthoquinones and dinaphtho[1,2-b;2′,1′-d]furans, utilizing an oxidative reaction via electron donor–acceptor complexes of 1-naphthols with SnCl4 in the absence or presence of dioxygen. As an application of this method to natural product synthesis, we describe a facile biomimetic synthesis of several binaphthoquinones, 3,3′-bijuglone, 3,3′-biplumbagin and elliptinone.

The asymmetric reaction of a lithium enolate generated from a BHA (2, 6-di-tert-buty-4-methoxyphenyl) propanoate was allowed to react with benzaldehyde in the presence of a diether-type chiral ligand affording the corresponding anti-aldol product in a moderate enantioselectivity. A tetradentate ligand induced better enantioselectivity albeit relative loss of anti-selectivity. A variation of lithiating amide agent affected the selectivity, indicating involvement of an amine as a component of the mixed aggregate. Absolute configuration of some of the aldol products was determined by standard transformations.

The chiral ligand controlled asymmetric conjugate addition reaction of lithium N-allyl-N-(tert-butyldimethylsilyl)amide to alkenoates proceeded smoothly to give, after protodesilylation, the corresponding 3-allylaminoalkanoates with high enantioselectivities in high yields. The allyl group on the nitrogen atom was easily removable to afford 3-aminoalkanoates.