Biguanides (phenoformin) have not been recently used to treat patients because of a high frequency of lactic acidosis (0.25-1 case per 1, 000 patients-years) and related deaths. The latest reports have stressed that biguanides metformin has no effect on pancreatic insulin secretion, including the decreased intestinal absorption of glucose, decreased glucose production in the liver, and improved lipid profile and, as a result, this drug is now being reevaluated. A retrospective study was carried out to assess the clinical effect of metformin in medication counseling. Using diabetic (NIDDM) outpatients whose treatment included the administration of metformin, the authors conducted a survey on the results of glycemic controls, weights, and serum lipid levels before and after an 8-week administration of the drug based on the patients' medical records at Aichi Medical University Hospital. The subjects consisted of a metformin group (M group; 10 cases) in whom the drug alone administrated as an antihyperglycemic agent. The results of this group were comparde wih those of a group receiving metformin in combination with sufonylureas (MS group ; 12 cases) based on a statistical analysis of the relevant factors. In the M group, the HbAlc concentration did not change (from 8.3±1.2% to 8.3±1.4%), but the HDL-C level significantly decreased (p<0.05). The MS group showed that the HbAlc concentration (from 9.9±2% to 8.8±1.4%), TG level, and HDL-C level all significantly improved (p< 0.05). The body weight and the serum lactic acid level were not significantly changed in either group before and after the administration of metformin. The results of this investigation indicated that metformin may thus be useful as an add-on therapy in patients with diabetes controlled by sulfonylu reas. In addition, it is particularly effective in obese patients with insulin resistance while also having a favorable impact on the lipid profiles.

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The purpose of this study is to investigate the clearance of theophylline (THCL) by specific factors which could affect THCL including smoking, concurrent drug use, and congestive heart failure (CHF), in pneumoconiosis outpatients over the age of 59, as well as the relationship between THCL and the values of respiratory function tests.
The subject population, which consisted of patients who were administered theophyllines, consisted of a smoking group, a concurrent drug use (certain drugs decreasing THCL on packageinsert drug information) group, a CHF group, and a control group.
The results of our analysis showed the THCL level in the smoking group to be significantly higher than that in the other groups (p<0.05). The THCL level also showed a significantly positive correlation with the % vital capacity (%VC) (r=0.668, p<0.05) and forced expiratory volume at 1 second (r=0.521.n.s).
The main finding of this study is that smoking was closely related to THCL in pneumoconiosis patients, and smoking induced a theophylline matabolism even in the elderly. The respiratory function correlated positively with THCL. Moreover, the %VC was also suggested to be useful for the THCL variability index.

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The side effects of nitrate patch preparations for ischemic heart disease were evaluated in both inpatients and volunteers. Therefore, a removal test of horny cells, adhesion test and down rolling ball (tack) test were all studied to clarify the pharmaceutical characteristics of these preparations. As a result, the score of the skin irritation of the NitrodermTTS^® preparation was significantly higher than that for the other two preparations (Antup^® and Frandol tape S^® preparation).
No correlations were observed between skin irritation and the amount of horny cells removed by the NitrodermTTS^®. The Antup^® preparation was the strongest for the adhesion test. However, the NitrodermTTS^® preparation was the strongest for the tack test. These findings suggest that one reason for the increased skin irritation of NitrodermTTS^® may be due to its high degree tack influence.

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The aim of this study was to compare iopamidol 370 mg I/mL with iomeprol 400 mg I/mL, regarding the incidence of immediate and delayed adverse reactions to the contrast media in patients receiving such drugs for coronary angiography. A total of 4298 patinets participated in the study consisting of 2203 and 2093 patients in the iopamidol and iomeprol groups, respectively. The incidence of adverse reactions was determined by assessing the number of patients with immediate adverse reactions (up to 60 min after drug administration) and delayed adverse reactions (within 14 days after under goin angiography). The immediate adverse reactions were monitored during and after the completion of drug administration, and delayed adverse reactions were surveyed by questionnaire over the telephone. There was no significant difference in the incidence of immediate adverse reactions between both drug groups: 6.4% for iopamidol vs. 6.3% for iomeprol. On the other hand, the incidence of delayed adverse reactions in the iomeprol-treated group (7.3%) was significantly less than that in iopamidol-treated group (9.1%). The incidence of delayed adverse reactions of patients with renal dysfunction (Serum creatine 1.5 mg/dL) in the iomeprol-treated group (41.3%) was also lower than that in the iopamidol-treated group (55.2%). These results showed no obvious difference in the incidence of immediate adverse reactions between the two groups, while the incidence of delayed adverse reactions was lower in the iomeprol-treated group, thus suggesting that the usage of iomeprol with a low osmolality was more useful in protecting patients with renal dysfunction from adverse reactions induced by contrast media.

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A study on the prevention of angialgia induced by the high osmotic pressure of Peripheral Parenteral Nutrition infusion: Influence on the infusion system using Tandem method.
During peripheral parenteral nutrition (PPN) infusions, angialgia more frequently occures than during other types of peripheral infusion. This is probably caused by the low pH, infusion speed and high osmotic pressure of PPN. We hypothesized that we could prevent angialgia by attenuating the osmotic pressures during PPN infusion. We therefore attempted examinations using the Tandem method as follows; It was possible to control the osmotic pressure in the effuent solution by changing the joining method of these infusions, thus suggesting that the specific gravity of these infusions affected the osmotic pressure.
Specifically, we connected a hypotonic infusions (e.q., Soldem-3 A) with a low specific gravity to a PPN infusion (e.q., Amicaliq) with a high specific gravity, and the osmotic pressure of the effluent solution was maintained at a high level during the first 15 min, but thereafter gradually decreased. On the other hand, We connected a PPN infusion to a hypotonic infusion, and thus were able to maintain a low and constant osmotic pressure in the effluent solution.
These results suggest that the Tandem method is useful in preventing angialgia due to the high osmotic pressure of PPN infusion. PPN infusion should thus be connected to a hypotonic infusion that has a lower specific gravity than that of the PPN infusion.

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To elucidate the current status of the dosage regimen of vancomycin, we reviewed its therapeutic drug monitoring (TDM) data obtained from 99 patients undergoing vancomycin treatment at the Chugoku Rousai Hospital. The plasma concentrations of vancomycin at one dosage under 750 mg deviated from its therapeutic ranges (the level at one hour after the end of infusion: 25-40μg/mL, trough level:≤10 μg/mL). Therefore, the dosing interval at a uniform dosage of 1000 mg was calculated from a vancomycin nomogram reported by Moellering et al., and the utility of the dosing interval at the uniform dosage of 1000 mg combined with a creatinine clearance nomogram reported by Nielsen et al. was examined. As a result, the plasma levels of 66 percent of the subjects were controlled within the accepted therapeutic ranges in the early stage. Accordingly, the nomogram of vancomycin prepared as an indication in the early stage in our hospital was thus concluded to be clinically acceptable.

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At Nagoya University Hospitald to increase the QOL in patients suffering from pain, we prepare a gargle containing Varidase^® and Xylocaine^® for the treatment of stomatitis during cancer chemotherapy. The gargle contained sodium azulene sulfonate, lidocaine hydrochloride, Varidase (mixture of streptokinase and streptodornase), and hydroxypropylmethyl-cellulose in distilled water. We evaluated the effect of the gargle on stomatitis patients. In this study, we adjusted the concentration of lidocaine (0.12, 0.24, 0.60, and 1.00 mg/mL of water) to control the pain induced by different degrees of stomatitis. We determined the appropriate concentrations of lidocaine in the gargle to be 0.24, 0.60, and 0.60-1.00 mg/mL, for mild, moderate and severe cases of stomatitis, respectively. After the most suitable concentration of lidocaine in the gargle was determined, the treatment was continued. We analyzed the relationship between the total amount of gargle and the effects of treatment on stomatitis. The treatment periods for stomatitis were shortened by increasing the total amount of gargle, in other words, the patients used the gargle at more frequent intervals per day. Based on these findings gargle containing Varidase and Xylocaine is therefore cinsidered be effective for the treatment of stomatitis.

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The adopted medicines in Suibarago Hospital were studied to be valid by the calculation of the selection index (SI) in each medicine group classified into pharmacological categories. The SI value means the number of medicines which can be chosen among 100 prescriptions per day and was calculated by the formula (=the number of the medicines in each medicine group/the logical number of prescriptions for one day×100).
The results were as follows; The antibacterial drugs excent the antibiotics had the highest SI value, when broken down into large pharmacological categories. In addition, antiepileptics, such as cephem antibiotics and psychoneurotics also had high SI values, when broken down into small pharmacological categories. Furthermore, the departments of internal medicine, orthopedics, gynecology had high SI values, when broken down into department categories.
If a SI value rises, then the selectivity of the medicine group is increased, but otherwise the medicine group is increased. On the other hand, the purchasing rate of the medicine group is decreased, as it tends to be against clinical needs. Therefore, our results indicate that we should reconsider both the validity of medicine groups showing high SI values and the proper distribution of medicines showing high SI values.

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The directions printed on a medicine bag should be easy to read so that patients will take their medicines occurately. The objective of this study was to identify what type of characters were the most preferable for reading printed directions. We interviewed 100 neurological patients, aged from 23-94 years, asking about their choice of font, size and color of print. We also asked for their preference in the writing of the three types of Japanese characters, hiragana, katakana, and kanji (Chinese characters).
All of the patients chose Gothic-type characters as the best font. Among the three Japanese characters, 79% preferred kanji, while only 7% and 2% chose hiragana, and katakana, respectively. The patients preferred black, blue and red colored prints in order. The patients were able to read 14-point sized Gothic-type characters, without any difficulty.
Our study suggests the directions should be written in kanji characters, especially printed with a Gothic-type font at least 14-point size.

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We investigated the stability of “Chloral Hydrate Syrup” by ¹H-NMR spectrometry and spectrophotometry.
“Choloral Hydrate Syrup” is composed of 4%(w/v) chloral hydrate, 50%(w/v) simple syrup and 2%(w/v) pineapple flavor. When “Chloral Hydrate Syrup” was kept in the dark and cold conditions, chloral hydrate was found to be stable for at least 2 weeks. No changes in the smell and taste of “Chloral Hydrate Syrup” were observed. However, the color was fugitive, and 80% of original color was lost within a week even in the dark and cold conditions.
The Pharmacological effects of “Chloral Hydrate Syrup” given for 25 infant patients, who had been hospitalized in Toyama Medical and Pharmaceutical University Hospital between September and November 1997, were evaluated clinically. “Chloral Hydrate Syrup” showed a certain, hypnotic effect in 24 out of 25 patients. These results suggest that “Chloral Hydrate Syrup” is useful as a hospital hypnotic preparation.

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In recent years, the higher quality has been increasingly required on pharmaceutical management and counseling services.
Nowadays the POS (Problem-Oriented System) has been establshed for the purpose. On the other hand, the clinical pharmacy diagnosis is considered to be an effective problem-solving tool in pharmaceutical care.
We therefore prepared a database for pharmacy diagnosis, problems, and care, using commercial application software called “KIRI, ” and designed a support system for pharmaceutical management and counseling services. According to this method, various documents, such as a probleme list, can be printed out on demand. By using this system, it is possible to reduce the number a disagreements among pharmacists. Moreover, these results also show that pharmaceutical care can be provided to patients to at a stable-level.

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A four-week training program in the Department of Hospital Pharmacy at the Toyama Medical and Pharmaceutical University was started two years ago. We accepted 109 undergraduates last year. In 1998, we introduced a one week clinical pharmacy practice into this curriculum. Pairs of students took charge of in-patients and studied examinatios, treatment and medication. At the end of this program, the students presented a summary of their case studies from the viewpoint of clinical pharmaceutics. We evaluated this program using questionnaires to determine the effect of the newly introduced clinical pharmacy practice and to improve the curriculum. The results of the survey showed that many students were interested in clinical pharmacy training and suggested expanding this program even further.
Questionnaires distributed to the managers of other hospital pharmacies and local drugstores showed that almost half of them wanted to participate and receive undergraduates in their pharmacy. In addition, most also wanted to hire such students who had experience in the clinical pharmacy practice.
Although many students have high expectations for clinical pharmacy practice, pharmacists in the hospital do not have enough time to sufficiently take care of students. An educational program of clinical pharmacy practice for undergraduate students in the Pharmaceutical University is therefore important to bridge this gap. We expect that this curriculum could be further improved by introducing educational visits and surveying practices at other hospitals and drugstores.

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Carvedilol, a nonselective β-blocking agent, has been widely used in the treatment of hypertension, and angina pectoris. It is subject to an extensive hepatic first-pass metabolism following oral administration, with a reported systemic bioavailability of between 22 and 24%. Since it is commercially available only in tablet form, the rectum is an effective administration method for elderly patients and for whom it is difficult to swallow tablets. For this reason the rectal absorption of carvedilol was studied in rats.
The plasma carvedilol levels were found to be significantly higher than the oral administration levels at 15 min, 1, 4, 6, 8, 12 and 24 hr after the rectal administration of 20 mg/kg carvedilol. In addition, the drug pharmacokinetic parameters, comprising maximum plasma concentration (C_max) was 1.7 times higher, and area under the concentration-time curve up to 24 hours (AUC_0-24) was 2.2 times higher after rectal administration. In comparison to the AUC_0-24 values, the relative bioavailability of carvedilol after oral administration was 19.3% and also after rectal administration was 42.2%.
These results are thought to be caused by a reduced first-pass metabolism, and the rectum was thus conformed to be an effective administration route for calvedilol.

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The Yamaguchi Hospital Pharmacists Association published a “Cheking Manual for Dispensing Injectable Drugs” in February 1998 after an 8-year evaluation so that pharmacists can contribute to the appropriate use of injectable drugs as a member of a health care team. This manual includes not only a checklist for such factors at the time of dispensing and the dose and administrative method, but also provides data on incompatibility (visual changes and decomposition). We evaluated the utility of this manual by a questionnaire survey. Inquires by physicians and nurses were the most frequently observed. Concerning the contents of such inquiries, inquiries about incompatibility accounted for about 73%, of which 72% could be responded to using this manual alone. Of all references made to this manual, 89% were contained in this manual. These results suggest that this manual adequately contributed to the appropriate use of injectable drugs.

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Many dispensed prescriptions are stocked in individial hospitals and pharmacies. If these prescriptions are collected at a center from various areas through an interne system, a large database for prescriptions can be developed. Using this database, pharmacy students, medical students, pharmacists and medical doctors will thereby be able to determine the best use of such medicines.
In order to develop a large database of prescriptions which can be used for various purposes, we made a small database, as a first step, on a personal computer by collecting dispensed prescriptions provided from a few pharmacies. From this database, general data related to patients and the medicines used was collected and, as a model example, the use of so-called “anti-dementia drugs” was examined.

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