The effect of anti-hyperlipidemic agent fenofibrate on the fasting plasma glucose (FPG) levels was investigated. Twenty-one hyperlipidemia patients received fenofibrate therapy.
In non-diabetic patients and type II diabetes mellitus patients who did not receive sulfonylurea therapy, the FPG levels after the administration of fenofibrate did not change significantly before therapy. However, in type II diabetes mellitus patients receiving sulfonylurea therapy, the FPG levels significantly decreased from 206± 13.6mg/dL to 170±16.1mg/dL, 181±21.3mg/dL, and 163±15.2mg/dL in 4, 8 and 12 weeks, respectively.
The effect of age on the FPG levels after fenofibrate therapy was not demonstrated in adult patients, however, those levels in patients over the age of 65 decreased from 153±26.2mg/dL to 129±20.8mg/dL in 12 weeks.
Those results showed that the FPG levels decreased after a combination of fenofibrate and sulfonylurea in type II diabetes mellitus patients, and the decrease in the FPG levels after fenofibrate therapy was found to be affected by aging.

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Anthracyclines have been used to cure a variety of cancers, and they are one of the most effective anti-cancer drugs. However, due to the simultaneous occurrence of serious side effects, successful chemotherapy is difficult to administer in clinical cancer treatment. Therefore, to evaluate the side effects, we examined the influence of anthracycline derivatives, especially epirubicin (EPI), on the glucose secretion and cytotoxicity of anthracycline derivatives in primary culture of rat hepatocytes.
In this study, EPI reduced the spontaneous glucose secretion dose-dependently in a primary culture of rat hepatocytes. However, EPI enhanced the increased-secretion induced by glucagon, and the potency of such enhancement at low concentrations was stronger than that at high concentrations. In contrast, aclarubicin (ACL) reduced both the spontaneous glucose secretion and the increased-secretion. Furthermore, Anthracycline derivatives increased the lactate dehydrogenase (LDH) leakage both time- and dose-dependently, and the potency order was idarubicin≥ACL >daunorubicin> EPI. The degree of cytotoxicity as evaluated by measuring the glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) levels and by performing an MTT-assay was also similar to the results obtained for LDH leakage.
These results suggest that EPI stimulates the sensitivity of rat hepatocytes to other endogenous agents, and this influence may be involved in the degree of cytotoxicity for anthracycline derivatives.

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Follow-up case by telephone was conducted for the discharged patients, who had received the medication consulting services from clinical pharmacists of Kobe university hospital. In this trial, we focused on the patients in the Department of Circulation and Respiratory Diseases. The follow-up case by telephone was carried out from the time of discharge until the next visit (almost 2 weeks after discharge). The patients consisted of 30 men and 17 women (average age was 66.9 years old). By telephone, the following issues were questioned; 1 : medication compliance, 2 : side effects and/or the changes of physical condition, 3 : other issues (such a when an inappropriate use of medicine had been suspected during hospitalization). When the patients so desire they could come in for a check-up anytime. More than about 90% of patients reported to keep good medication compliance and to have no significant side effects. However, 34% of patients claimed a slight of change in their physical condition including dropsical swelling, boiling and gasping. The claims were found more frequency in patients who had been suspected of inappropriately taking their medication. Follow-up care by telephone was found to be an effective way to avoid any kind of risks including the discontinuation of medicine. As a result, although further examinations should be addressed, follow-up care by telephone appears to be a good way to ensure the appropriate use of medicine.

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The present study was aimed at establishing a method to evaluate the disintegration of commercially available rapidly-disintegrating tablets. We performed disintegration tests using three procedures based on JP XIV : using an accessory disk on the usual basket, not using an accessory disk on the usual basket, and using the Distopper^® which is an apparatus for recognizing the disintegration time using an electron sensor. The coefficient of variation (C.V.) values were over 20% in both the tests with and without an accessory disk on the usual basket, whereas those in the test using the Distopper^® were less than 20%. We next investigated the disintegration time of the tablets put on the tongue in five healthy volunteers. A significant correlation between the in vitro test using the Distopper^® and the in vivo test using the volunteers in the disintegration time was observed (r= 0.60, p< 0.05). The correlation increased when their disintegration times were limited to within 30 sec (r = 0.75, p< 0.001). These results suggest that the disintegration test of the rapidly-disintegrating tablets using the Distopper^® accurately reflects the disintegration profiles in the oral cavity.

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To enable the accurate application of the eye medication into an inpatient's eye during the recovery stages of treatment for cataract disease, an easy to use eye drop assisting device which can be operated with one hand was tested.
The device tested was pharmaceutically evaluated regarding such points as the ability for the eye medication container to be fixed onto the device, the ability to maintain a suitable height for the application while taking into account the length of the eyelashes, and the sense of comfort for the patient's face while using this device.
As a result, by making a slit on to the eye drop assisting device, the solution container could be easily fixed to the device. Furthermore, the findings indicated that the recommended height of the device should be 46mm.
Since this drop assisting device can be operated by one hand, it was determined that inpatients with ophthalmic disease could also use this device just the same as cataract inpatients do.

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To facilitate mutual understanding between doctors and nurses, prevent errors, and assure quality control in the mixing intravenous drip solutions at Ikeda Municipal Hospital, the Department of Pharmacy manages changes in the mixing of solutions and provides appropriate information for drug use. We mix solutions for intravenous injection under uniform standards and also set up a satellite pharmacy to perform these functions in April 2000. This satellite pharmacy accepts prescriptions for manual intravenous injections and manages two laminar air follow cabinets and a laminar flow biological safety cabinet. A ward trial was started in April, another ward was added in June and all wards were included in October 2000. We mix solutions for intravenous injection from Monday till Friday, based on prescriptions received the previous day, from four divisions. The hours of operation are from 10 : 00 Am to 8 : 00 Pm excluding weekends and holidays. The preparation of anticancer and narcotic drugs is not performed by the satellite pharmacy. We mixed 60 to 70 bottles of intravenous injections per day, over a six-month period. Of the intravenous injections mixed, about 70 percent were mixed by the Department of Pharmacy. 95.3 percent were used, 1.8 percent diverted, 2.9 percent were not used.

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Although many patients suffering from poisoning are treated in Kamamoto Red Cross Hospital, about half of them are babies and little children, and the most frequent cause is the accidental ingestion of cigarette butts. In principle, early poisoning treatment is done by washing out the stomach. Ipecac Syrup is used as a medicine to induce vomiting in Europe and America. This medicine has also become a popular household medicine. In our hospital we have been clinically using this syrup since 1987.
This report describes the clinical results of such cases and the effect of the syrup which has been prepared in our hospital for the past four years.
The syrup did not have particular side effects and was effective in more than 90 percent of the patients who had mistakenly ingested dangerous substances. The syrup was thus found to be safe and effective.
The accidental ingesting of cigarette butts is not considered to be a very serious medical problem. Less than 40 percent of such cases were treated by the induction of vomiting alone. However, the butts remained in the stomach of other patients. Nevertheless, the treatment of choice remains the induction of vomiting since stomach pumping (washing out) is stressful to the patient and also is more dangerous.

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Patients with cerebrovascular disease or rheumatoid arthritis and elderly persons are sometimes unable to easily push out tables from PTPs (Press Through Packages). As a result, a few special factors which may affect the pushing out strength of PTP and an ability of pushing out tables from the PTP were investigated. The pushing out strength of 10 products which might have a different pushing out strength of PTP was measured by the SHIMADZU AUTOGRAPH. In spite of an increase in the push out speed, the pushing out strength measured did not consequently change. The pushing out strength decreased when the diameter of the push-out equipment decreased in contrast to the ceiling diameter of the pocket. This result suggests that the pressure inside the diameter of the pocket of the PTP makes the opening of the PTP easy.
The pushing out strength decreased when the thickness of the tablet was increased, and when the thickness of the PVC in the center of pocket decreased. The pushing out strength measurement and the opening test score of the PTP by the cerebrovascular disease patients yielded a negative correlation. It is therefore important to develop new PTPs in which it is easier for patients to push out the tablets using this measurement method of pushing out strength.

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We studied the effect of total-vitamin addition, insulin concentration and the exchange of infusion containers on the adsorption of insulin to infusion containers and infusion sets (line and filter). The adsorption of insulin to infusion containers and infusion sets decreased by the addition of total-vitamin injection, and the addition of a half-volume of total-vitamin injection also gave a similar result.
In the absence of total-vitamin injection, adsorption to the infusion containers was not influenced by the concentrations of insulin (5-40 units). However, the adsorption to infusion sets decreased as the concentration of insulin increased. In the presence of total-vitamin injection, adsorption to infusion containers and infusion sets decreased by the same degree, but was not influenced by the change in concentrations of insulin (5-40units).
When the infusion container without total-vitamin injection was changed to a new one with total-vitamin injection, a rapid increase in the insulin outflow of the infusion set was observed. The increase in the insulin outflow could be prevented by the addition of a half-volume of total-vitamin injection into both infusion containers. These results suggest that the constant addition of a half-volume of total-vitamin injection containing surfactants into each infusion container is an effective way to slightly change the insulin outflow of infusion set when two containers a day are needed.

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During a three-week long practical training program for pharmacy students at our hospital, senior pharmacy students had a one-day observation of pharmacists performing new drug investigations. Using a questionnaire survey we investigated whether the observation of the work of clinical research coordinator (CRC) influenced the student's understanding of the new drug investigation procedures. The observation of CRC's work consisted of counseling/interviewing prior to the doctor's consultation and visiting a clinical laboratory to observe new drug investigations. The items evaluated were impressions of the clinical investigation of new drugs, precautions for preparing investigational drugs, understanding the new Good Clinical Practice (GCP) guidelines and other important aspects in the clinical investigation. Each group consisted of 26 students. Only 10 out of 26 students observed counseling/interviewing before the doctor's consultation with CRC. The impression of the clinical investigation procedure in group I, which observed the CRC's work was more favorable than in group II, which did not observe it. The understanding of the important aspects of the clinical investigation procedures in group I was markedly better than in group II. We thus consider that the observation of the CRC work is very useful for students not only to learn new drug investigation procedures, but also to understand the meaning of the new GCP guidelines.

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The Theophylline (TP) doses, blood TP concentrations and hospitalization duration of patients examined in our hospital due to asthmatic attacks were investigated to determine the usefulness of TDM. A high noncompliance rate was hypothesized in patients with blood TP concentrations of less than 10μg/mL at the time of asthmatic attacks. For such patients, it is important to increase the blood TP concentration to above 10μg/mL as soon as possible, and instructions on how to take the medicine should be given when they visit the outpatient clinic. For patients with blood TP concentrations of more than 10μg/mL at the time of asthmatic attacks, care should be taken not to prescribe an overdose of TP, and other treatment methods should also be consisted. These results show that hospitalization and TP intoxication can be avoided by appropriately performing TDM for asthmatic patients.

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To supply drug information using documents is very important to ensure patient safety and the proper use of prescribed drugs. Such documents should include easily understandable information for patients. In the development process of drug information leaflets at our hospital, we incorporated reviews of the documents made by normal individuals and not medical professionals. It was found that more than 100 of descriptions in the documents were given in language that was too technical to be understood by normal individuals. Approximately half of these descriptions were related to “drug effects”. We reviewed the information for 500 of 997 drugs using supplementary interpretations and more conventional expressions to make the drug information leaflets more intelligible.
Acceptability of the leaflets by patients was evaluated based on a questionnaire survey to which 300 outpatients responded. As a result, most of the patients reported that the “drug effects” and “initial symptoms of adverse reactions” in the documents were easy to understand by 89% and 81 % of the patients, respectively.
From these results, our drug information service using more intelligible leaflets was found to effectively promote a better understanding of prescribed drugs, thus leading to their safe and proper use.

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To examine the frequency of developing a dry cough due to angiotensin-converting enzyme (ACE) inhibitors and its affecting factors, 134 inpatients receiving ACE inhibitors were interviewed to clarify whether or not they experienced dry cough, as a part of pharmaceutical consultations. One pharmacist conducted all interviews to avoid any biased impression of the patients. The development of dry cough was observed in 34 patients (26. 1%), and severe dry cough was noted in 9 patients. The frequency of the development was much higher than that described in the Interview Form provided by the pharmaceutical companies. The development of dry cough was not affected by the gender or age of the patients, and no relationship was found with the daily dosage of ACE inhibitors, smoking habit, the presence of pulmonary disease and the co-administration with drugs influencing the respiratory function. However, the incidence of dry cough induced by the administration of perindopril was significantly higher than that induced by enalapril, and dry cough tended to develop at night. In addition, the incidence of dry cough in the patient group who understood the presence of dry cough as a side effect was significantly higher than that in the group without such knowledge.. However, the complete disappearance of dry cough could be achieved in all patients by changing the medication to angiotensin II receptor antagonists based on the proposal of the pharmacists.
These results suggest that there is a difference in the development of dry cough among individual ACE inhibitors, and the incidence is, at least partly, dependent upon the comprehension levels and the psychological state of the patient. The present examination should be of clinical importance since it can help patients obtain proper drug therapy by the early detection of adverse effects.

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Aspirin is widely used as an antiplatelet drug for the secondary prevention of cardiovascular event in patients with myocardial infarction. However, gastrointestinal complications (ulceration, bleeding, perforation) as adverse drug reactions may also be associated with aspirin use. Low-dose aspirin is very widely used for the secondary prevention of cardiovascular event that clinicians may not be aware of gastrointestinal complications. We report 5 patients with gastrointestinal bleeding associated with low-dose aspirin for the prevention of cardiovascular events.
All 5 patients were males, and the mean age was 68 ± 9.6 years. They had been treated with low-dose aspirin (81mg daily) from 17 days-2 years. At hospital admission, all patients had severe anemia, and complained of anorexia, tarry stool, melena, and light-headedness, but none reported stomachache. A gastroendoscopic examination showed active A 1 stage ulcers in four patients, and an active A 2 stage ulcer in one patient. Endoscopic hemostatic procedures were performed in four patients. In all patients, the gastrointestinal complications improved after the administration of proton pump inhibitor and the discontinuation of aspirin.
Although every patient had been administered low-dose aspirin (81mg daily), severe gastrointestinal bleeding which required hospitalization developed in all 5 patients. They did not complain of pain, and their hemorrhagic ulcers were suspected to be due to severe anemia or melena. Their symptoms were consistent with the features of “silent ulcer” associated with aspirin or other nonsteroidal antiinflammatory drugs. All but one patient was elderly and more than 60 years of age. In 3 patients, hemorrhagic ulcers developed within 2 months after aspirin initiation. Therefore, gastrointestinal bleeding associated with aspirin does not necessary occur only after long term use.
When aspirin is used for the secondary prevention of cardiovascular events in patients with myocardial infarction, the risk of gastrointestinal bleeding can not be ruled out even with low-dose administration. Especially for elderly patients, clinicians should therefore include such a possibility in the follow-up of such patients.

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