Dietary supplements are gaining wide popularity in Japan and are used by a large number of patients as self-medication. Though dietary supplements cannot be considered as drugs, patients expect pharmacological benefits from them since they usually have very little knowledge of their effects. Thus, pharmacists have the responsibility to expand their knowledge of dietary supplements so that they can give better advice to patients who are using them. However, only a limited amount of information on dietary supplements is available to pharmacists.
In the present study, we evaluated the content and solubility of coenzyme Q10 (ubidecarenone, CoQ10) in dietary supplements. CoQ10 is not only used as a dietary supplement, it is also prescribed as a drug by physicians. CoQ10 preparations were ground up and various techniques were used to extract the active ingredient, among them extraction using solvents, ultrasonication and heat. We found that the prescription drug preparations containing CoQ10, both original and generic products, had exactly the same content as stated on the label and had good solubility. Though dietary supplements containing CoQ10 also had the exact content stated on their labels, they showed poor solubility. Such poor solubility would give rise to major differences in elution and bioavailability between dietary supplements and prescription drugs containing CoQ10.

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Despite intensive treatment with standard methods, recurrent malignant gliomas (specifically, anaplastic astrocytoma and glioblastoma multiforme) have a poor prognosis. Thus, new treatment strategies that address the issues of symptom control, curtailing progression and overall survival are urgently needed.
In this regard, Temozolomide (TEMODER, TMZ) is a novel, oral alkylating agent which has been approved for the treatment of patients with recurrent malignant glioma in many countries, though not in Japan. The effects of TMZ were investigated in patients (n=10) with glioblastoma multiforme, anaplastic astrocytoma, or anaplastic oligodendroglioma. TMZ achieved high rates for partial response (20%) and disease stabilization (50%). Also, there was a positive correlation between the clinical response to TMZ and Karnofsky performance status (KPS) before treatment with TMZ, but not with the number of other treatments given before treatment with TMZ. The major adverse events were anorexia (40%), diarrhea (30%), and somnolence (40%).
In view of its dependable safety profile, clinical efficacy, and convenient dosing, TMZ could be an effective therapy that provides important quality-of-life benefits for Japanese patients with recurrent malignant glioma.

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Nitorol^® Injection is commercially available in glass bottles and ampoules. As it is often used in emergencies such as angina attacks and myocardial infarction, there has been a clinical need to develop a soft bag preparation. However, since the drug adsorbs onto the bag material, the development of a soft bag preparation had been considered impossible.
In recent years however, success was achieved in developing a soft bag preparation (Nitorol^® Injection Bag), and we assessed its usefulness in the clinical setting. In order to do this, pharmacists in our hospital compared preparatory procedures for administration between the bag and other administration forms, and a questionnaire was distributed to doctors, nurses, and pharmacists in order to investigate their opinions regarding safety, ease of use, risks, and cost.
The results of our assessment showed that the preparatory procedures for the administration of Nitorol^® Injection Bag were simpler than those for the Nitorol^® ampoule, which reduced risks, and regarding container material and container disposal costs, Nitorol^® Injection Bag was more economical. Further, the results of our questionnaire survey showed that Nitorol^® Injection Bag was superior in terms of safety, ease of use, and its convenience overall was highly rated.

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Several methods have been used for achieving good medication compliance-among them one-dose packages, self reporting diaries, and measurement of drug serum concentrations-but such methods are all insufficient for clinical purposes. The aim of this study was to assess the usefulness of a newly developed electronic device for medication compliance (compliance recorder) through the monitoring of daily compliance in patients with hyperlipidemia.
Eight patients (mean age : 64 years old, range 57 to 73) taking pravastatin (10 mg/once a day) were randomly assigned to 2 groups-an intervention group for which the electronic compliance recorder was used to evaluate compliance data and a control group not using the recorder. Both groups were checked for total cholesterol and LDL-cholesterol levels on each day hospital visit day, and thereafter compliance was checked through self reporting at the community pharmacy.
All data were retrieved from the electronic compliance recorders in the observation periods, the mean of which was 180 days (range 168 to 196 days). The compliance rate calculated for the intervention group was 96.5 % (718 patients days). For the total cholesterol and LDL-cholesterol levels, there were no statistically significant differences between the two groups in the observation periods. From the self-reporting scores, the intervention group maintained good compliance throughout the observation periods.
These results suggest that the electronic compliance recorder is a useful tool for improving compliance.

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It is important to assess the immunity of health care workers against the measles, rubella, mumps and varicella viruses and to raise their immunity through vaccination. We evaluated the immunity of all staff of the Yamagata University hospital and Yamagata University, School of Medicine (total 890 350 males, 540 females) through the measurement of serum IgG specific for the measles, rubella, mumps and varicella viruses by the ELISA assay.
Performing these measurements showed that the antibody negative rates of the health care staff were 9.1% for measles virus, 9.6% for rubella virus, 15.2% for mumps virus and 0.6% for varicella virus. These rates were higher in specific age groups with antibody-negative rates increasing to 17.5 % in the 21-30 age group for measles virus, 13.2% in the 41-50 age group for rubella virus and 20.7% in the 31-40 age group for mumps virus. As for the varicella virus, 4 persons in the 21-30 age group were negative for antibodies and 1 person was negative in the 31-40 age group. There were also differences between the sexes in frequencies of antibody-negative persons, especially for the rubella and mumps viruses.
More males tended to lack immunity than females.
Based on these results, we recommend vaccination against these viruses for the staff concerned.

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We investigated the change in drug concentrations in serum stored in sterilized vacuum tubes for serum separation. The serum concentrations of seven drugs-phenytoin, phenobarbital, carbamazepine, vancomycin, valproate, theophylline and digoxin-were determined after storage in three different vacuum tubes-Vacutainer^® SST and SST II (SST, SST II, Becton Dickinson Co. Ltd.) and Neo-Tube^® GP-SP 1029 (GP-SP, Nipro Co.). Though there was no change in the serum drug concentrations for any of the tested drugs in GP-SP, the concentrations of phenytoin, phenobarbital and carbamazepine in the serum stored in SST and SST II were significantly decreased due to adsorption onto the serum separator. The degree of adsorption was greater for the SST tube than the SST II tube and for the drugs, the order of adsorption was phenytoin>carbamazepine>phenobarbital. The adsorption of phenytoin onto the separator of SST depended on several storage conditions, such as initial drug concentration, storage temperature and storage volume, while its adsorption onto the SST II separator depended on storage temperature and storage volume. In addition, the change in phenytoin concentration during storage in the SST tube was well correlated with the free fraction of the drug. This indicates that protein binding is an important factor affecting the stability of drug concentrations in serum stored in separation tubes.
Overall, the results of our study indicate that for accurate therapeutic drug monitoring, it is necessary to select vacuum serum separation tubes on the basis of drug concentration stability data for them.

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The early detection of adverse drug reactions and pharmaceutical treatment for them are important in ensuring that drugs are administered safely. However, it is not easy for pharmacists to monitor all prescribed drugs for adverse drug reactions. In view of this, we have established a screening system (drug safety management monitoring system) for any adverse effects that may have causal relationships with administered drugs and the screening results are fed back to the physicians in charge. The system compares current data with that stored in our clinical laboratory's data management registry and identifies laboratory tests significantly different from earlier ones. In the present study, we examined the reasons for 258 instances of abnormal changes in laboratory tests in 187 patients that we reported to attending physicians between April 2003 and March 2004. For 82 of the 258 instances, causal relationships with drugs could not be ruled out. Our pharmacists proposed prescriptions for the abnormal laboratory tests deemed to be adverse reactions and 44 % of them were accepted by the physicians in charge, in view of the importance of treating adverse drug reactions as early as possible.
In conclusion, we consider that our drug safety management monitoring system would to be useful for the early detection and treatment of adverse drug reactions.

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Some patients react very negatively to the introduction of self-injection with insulin into their treatment. This may be due to the fact that patients are not aware of the specific details of self-injection. Patients using oral hypoglycemic agents and those undergoing dietary and exercise therapy, and healthy persons with no history of diabetes mellitus were asked to answer 11 questions concerning their image of self-injection, before and after they were given information on pen-shaped injectors and other information concerning self-injection with insulin. From the responses, we investigated changes in their attitudes toward self-injection due to the information they were given. A factor analysis of the responses revealed that there were two major factors in the resistance to self-injection : a feeling that self-injection was troublesome and the social discomfort of injecting. These results suggest that provision of specific information prior to the introduction of self-injection insulin would be useful in reducing resistance towards it.

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There have been very few studies on the efficacy and safety of subcutaneous morphine “rescue doses” in patients being treated with continuous subcutaneous infusion of morphine for the management of cancer pain.
In order to evaluate the safety and efficacy of subcutaneous morphine rescue doses as an adjunct to a continuous subcutaneous basal infusion, we investigated the dosage range of the morphine rescue doses, the ratio of their dosage to the 24-hour baseline dosage, the change in pain score and adverse effects for 31 subcutaneous morphine rescue doses administered to 10 cancer patients, who were admitted to the Shizuoka Cancer Center over the 11-month period from April 2003 to February 2004.
As for the findings, the 24-hour baseline dose of morphine was 46.72±35.99 mg and the smallest and largest rescue doses were 0.4 mg and 8 mg, respectively. All of the rescue doses were equivalent to 4.16% of the 24-hour baseline dose. Following rescue doses, the pain score significantly decreased from 6.27±2.49 to 3.10±2.80 (p<0.001) and of the 31 rescue doses administered, 25 produced no adverse effects. In a few patients, the rescue doses brought on or exacerbated nausea/and or vomiting, (n=3), caused drowsiness (n=2) or dry mouth (n=1).
These results suggest that a subcutaneous morphine rescue dose equivalent to 4.16% of the 24-hour baseline dose of a continuous subcutaneous morphine infusion can significantly reduce pain and that adverse effects such as nausea, vomiting, drowsiness and dry mouth only occur in a few patients.

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Cyclosoprin A (CYA) has been shown to be a potent immunosuppressive drug, and it has been administered as eye drops for penetrating keratoplasty and severe allergic conjunctivitis. In this study, we investigated the pharmaceutical characteristics of 0.05 % CYA aqueous eye drops using α-cyclodextrin as a solvent (CYA-CD eye drops) and their topical application for uveitis and scleritis in the clinical setting.
The pH of the CYA-CD eye drops was about 5.1 and in dark storage at 4°C for a period of 10 months from preparation, there was no change in pH or the CYA concentration of the CYA-CD eye drops. When the partition coefficients of CYA were measured in 1-octanol/water, this parameter (log P_oct/w) was 2.16 for the CYA-CD eye drops. This value is similar to those for CYA in the literature showing that the release behavior of CYA in the CYA-CD eye drops was not influenced by CD. Therefore, the CYA in CYA-CD eye drops would be rapidly taken up by the cornea.
When the CYA-CD eye drops were clinically applied in 12 patients with uveitis and scleritis, they were effective in 10 patients enabling them to reduce the dosage of steroid eye drops they were taking or stop using them altogether, showing that CYA-CD eye drops are effective for these conditions.

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We have been collecting data on the adverse effects of chemotherapy in our hospital and analysing it, and based on our analysis of adverse effect data for acute myelogenous leukemia patients, we prepared a brochure entitled “Explanation of the adverse effects of high dose Ara-C chemotherapy”. We then used a questionnaire to ascertain patients' impressions of our brochure. From the results, we noted that it could reduce the anxiety that patients felt towards the chemotherapy and enabled them to prepare themselves for the adverse effects. We are sure that this kind of activity will help us to provide better pharmaceutical care for patients.

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The results of cancer chemotherapy have been improved remarkably by the development of new drugs and combining drugs in treatment. However, cancer chemotherapy protocols are complicated and the adverse effects are more severe than those of other pharmacotherapies. It was therefore felt important to create a database of protocols for the preparation and dispensing of drugs used in cancer chemotherapy.
Using Microsoft Access, we have created a database from 320 protocols we have collected so far from 12 clinical departments and developed operating programs for it. The database has enabled us to search for a protocol using keywords-names of drugs, diseases and clinical departments-and most of the operations can be carried out by the click of a mouse. With our database, pharmacists are able to access protocols quickly and check prescriptions of anticancer drugs even if they are unfamiliar with computers, and we consider it to be a useful tool for this purpose.

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Hange-koboku-to (Banxia-houpo-tang), a Traditional Chinese Medicine remedy, has been used to treat swallowing reflex disorder, and it has been recently suggested that one of the mechanisms for the empirical effect of Hange-koboku-to involves humoral changes in neuropeptide levels. We suggested to administer Hange-koboku-to to a 70-year-old man with swallowing reflex disorder due to multiple cerebral infarctions and investigated the relationship between changes in plasma-neuropeptide-like immunoactivity (LI) levels and swallowing for a period of 1 week. On the 4 th and 7 th day of administration, the patient' s plasma calcitonin gene-related peptide (CGRP) -LI levels were twice the concentration on day 0 and Hange-koboku-to had increased the patient' s plasma substance P-LI levels approximately 5-fold on these 2 days. The plasma substance P-LI levels on days 4 and 7 were close to the levels (mean±SD) of elderly subjects without swallowing reflex disorder. Following the administration of Hange-koboku-to, plasma somatostatin-LI and vasoactive intestinal polypeptide (VIP) -LI levels in this patient exceeded those of elderly subjects without swallowing reflex disorder (mean + SD). With regard to symptoms, the patient' s difficulty in swallowing had disappeared on the third day of administration.
This study suggests that Hange-koboku-to relieves swallowing reflex disorder by stimulating neuropeptidergic nerves and that this effect is achieved within 1 week of administration. However, we need to study more cases of the use of Hange-koboku-to for swallowing reflex disorder and further investigate the relationship between changes in neuropeptide-LI levels and its pharmacological effects.

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