Polylactic acid (PLA) microspheres containing theophylline as a slightly soluble representative drug were prepared using the o/w emulsion in-water drying method. A high trapping efficiency was observed when polymer solution of high concentration was used and the drug/polymer weight ratio was increased. However, the particle size of the microspheres became extremely large when the high concentration polymer solution was used.
Microspheres with a particle size of 88.6 μm were obtained when “ sub-emulsification” was performed with the external aqueous phase with an equal specific gravity to the polymer solution. On the other hand, the trapping efficiency of the microspheres was dependent on both the drug encapsulated in the microspheres and the particle size of microspheres.
The release patterns of the drug from the microspheres showed an initial-burst release in all batches. The release rates of the drug from the microspheres prepared with the drug and polymer alone were very small. Therefore, an improvement in the drug release property of the microspheres was examined.
The release rates of the drug from the microspheres increased si gnificantly depending on the amount of ethyl myristate that was incorporated as a release promoter.

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Although macrolide antibiotics are known to elicit a pharmacokinetic interaction with other various agents via the inhibition of oxidative metabolism by P 450, the inducibilities of druginteraction have yet to be quantitatively compared among various macrolides. To quantitatively compare these incidences, we collected the findings of various reports in order to analyze and integrate them retrospectively
.We chosed reports referring to the area under the curve (AUC) value in human after the oral administration of carbamazepine, cyclosporine, felodipine, midazolam or terfenadine, which is known to be metabolized by P 450 3 A 4, alone and with macrolides. The decreases in oral clearance (ΔCLp. o.) evoked by macrolides were calculated according to the increase in AUC by the concomitant administration of macrolides.
In the 23 collected reports, erythromycin (EM), clarithromycin (CAM), azithromycin (AZM), miocamycin (MDM) and roxithromycin (RXM) were referred to in 13, 2, 6, 2 and 2 reports, respectively. Other macrolides, were only referred to in one report. The ACLp.o. values of the five macrolides noted above, i. e. EM, CAM, AZM, MDM and RXM were 51.0±18.1, 66.3±8.1, 5.8±13.6, 29.4±23.5 and 11.1±29.5%(mean±S. D.), respectively. The ACLp. o. that of AZM was significantly smaller than of EM and CAM (p< 0.001 and p< 0.01, respectively ; by ANOVA and Bonferroni multiple comparison test).
In conclusion, based on a retrospective analysis of the pharmacokinetic data in literature, AZM may be less effective for eliciting a pharmacokinetic drug-interaction. As a result, AZM might have some advantages over EM or CAM for avoiding of drug-interaction.

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We conducted a Study to establish a more effective way of providing drug-related information using a light emitting diode (LED) board at the waiting hall for outpatients to improve both the patients, interest in medication and the quality of medication consultation at the medication counter.
We provided various of information with characters as well as still and animated pictures in color on an LED board installed beside the electric bulletin board for finished prescription numbers at the waiting hall for outpatients.
Three kinds of information were presented; including in formation on patient education, general information on medication and recent topics on medication.
Of 253 outpatients, 86% noticed the existence of this information, which thus suggested that the information on the LED board had a good visibility. In addition, 80% of the patients understood the importance of the rational use of medication which 46% of the patients asked a pharmacist about their own medicine.
Furthermore, this method of providing drug-related information was be an effective means to make the patients aware that they should play a primary role in achieving successful pharmacotherapy, to improve their interest and understanding in medication, and to increase the degree of individualized medication consultation.

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The incidence of anemia was retrospectively studied in 47 patients treated with angiotensin converting enzyme inhibitors (ACEIs) over a one-year, period and the relation between the incidence of anemia and their renal function was examined. The ACEIs included enalapril, imidapril, lisinopril and temocapril. The serum creatinine levels in these patients were 0.5 to 3.1 mg/dl (1.1 ± 0.6, mean ± SD). The development of anemia was defined by a decrease in blood hemoglobin (Hb) of more than 1g/dl after ACEls.
The incidence of anemia was observed in 23.4% of 47 patients. The incidence was 14.3% in patients with a normal renal function. The incidence of anemia was higher in patients with a lower renal function.
Anemia occurred 8.7 ± 4.0 months (mean ± SD) after the start of ACEI treatment. During the same period, Hb decreased from 12.8 ± 2.4 to 11.3 2.5g/dl (mean ± SD), and hematocrit decreased from 39.1 ± 6.7 to 34.5 ± 6.6%(mean ± SD).
These results indicate that ACEIs induce anemia in patients without a severe renal function. Anemia should thus be carefully monitored during the treatment with ACEIs even in patients withouts severe renal dysfunction.

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We developed safe and simple closed system for preparing ointments containing cytotoxic drugs using a polyethylene bag.β-Carotene (β-C) and fluorescein sodium (FL) were used as model drugs in the present study. All preparation procedures were carried out in a polyethylene bag. The uniformity of drug content in the ointment was obtained by rolling the contents more than 20 times with a roller in both model drugs. The contents of each model drug in the ointment prepared by a closed system were consistent with those by the conventional method using a glass mortar. The time required to prepare the ointment in a closed system was much shorter than that using the conventional method. In addition, no contamination was observed in the closed system, whereas some contamination of the cyto-safe sheet and gloves with FL were observed with the conventional method. Based on the present findings, a closed system using a polyethylen bag is thus considered to be a useful method for preparing ointments containing cytotoxic drugs.

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The pharmacist should provide the patient with suflcient information, including any expected adverse effects, to ensure that the patient can safely and appropriately use medication. However, informing patients of possible adverse effects might also induce the patients not to take the medication. Therefore, in an attempt to facilitate the counseling about adverse reactions of the dispensed medicine, the effect of illustrating adverse reactions on the rational use of the medication was studied. A total of 125 types of drugs prescribed for 107 out-patients with rheumatoid arthritis (RA) were classified into two groups. One was a group in which consultation by the pharmacist is extremely important for (64%), and the other is the one in which such consultation is only moderately required (36%). The former group has potentially severe adverse reactions, frequent mild adverse reactions, or the ability to change the color of urine, stool, or tears. The illustration cards were developed and provided for 30 out-patients with RA. These patients were also counseled by the pharmacist about the adverse reactions listed in the card. This information trial was found to help relieve the anxiety in 57% of the patients, and to help patients understand adverse reactions in 77%. From these.results, in order to improve the clinical effectiveness and avoid the adverse effects of the medication, it is thus important to develop proper drug information cards which provide patients with correct knowledge on the adverse reactions for the patients.

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This study examined the actual condition on the use of beta-blocker eye drops, and the duplicated prescription of eye drops. Patients were thus surveyed on the rational use of beta-blocker eye drops carried out through personal interviews at our Pharmacy Department counter. The results showed that the practice rate of the “instillation of one drop of the eye drops” was 55 (78%) of 71 patients, while “eyelid closure for 1 minute after application” was 45%, and “nasolacrimal occlusion for 1 minute after application” was observed in 20%. The practice rates of “eyelid closure” and “nasolacrimal occlusion” were increased about 2 fold, respectively, as compared with the data obtained one year earlier. This may be due to the abouve extra consultation. However, these practice rates were still small. This indicates that many patients may be not fully aware of the importance of such practice. Therefore, further education will be needed to instruct patients in the rational use of the eye drops.
The results of prescription surveys in 6500 sheets for 3 months from November, 1995 to January, 1996 showed that the total number of over-prescription of beta-blocker eye drops and calcium antagonist internal medicine was found to be 105. These results show that we must constantly check for duplicated prescription to patients prescribed beta-blocker eye drops, while furthermore, comprehensive provision of drug information on the development and prevention of the systemic side effects of beta-blocker eye drops to oculists and physicians is also essential.

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The training program was designed to understand the activity of pharmacy through a practice program for fourth-year undergraduates studying at School of Medicine, University of Tsukuba.
We carried out a questionnaire survey which was given to students to objectively evaluate the training program. The results showed that almost all students found the pharmacy practice to be useful for their clinical training.

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The annual report about the prescription pattern of narcotic analgesia preparations in Akita University Hospital indicated that the total amount of morphine increased in an exponential way during the past decade and these finding also closely paralleled the increment ratio compared with the statistical data from the official publication in Japan. In order to understand the dosage and dosage form of morphine, and to study the clinical outlook for the highly increase in morphine therapy against various types of painful symptoms, we analyzed not only the utilization and prescription pattern of each preparation, but also the diagnostic criteria in patients who received morphine over the past two years.
Our results showed that 99.2% of amounts was given to 362 cancer patients that were composed of 87.5% of all patients and a few amount was prescribed to 137 patients who had been hospitalized due to acute circulatory episodes, congenital defects, and so on as a parenteral route. Metastasis or another types of carcinoma were found in 64.6%(234) of the cancer patients, and these multiple complications may be associated with the much higher doses and the changes in the dosage regimen among the different preparations. Although a large amount of morphine was given to a few patients with severe pain due to carcinoma of otorhinolaryngiological locus, the incidence of esophageal cancer was identified to be the most frequent type among the patients studied for a two years period.
It may be important to promote the appropriate administration of each morphine preparation and to support the continuous management for cancer patients according to the clinical or pathophysiological point of view due to the increased consumption of morphine.

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We studied the influence of in-line filtration with various types of filters on the delivery and distribution of particle diameter in the delivey of fat emulsion (10% and 20% Intralipos). The filtration rate of fat emulsion solely by gravity varied with the pore size (0.8 and 1.2 μm) and the materials (mixed esters of cellulose, posidyne nylon 66 and polyethersulfone of filters). The use of an IVEX-PF filter caused occlusion at the initial stage of infusion of fat emulsion. The filtration rate through TNA1 was much lower than those of the other 1.2 μm filters over the whole infusion period. This finding might be interpreted to occur due to the characteristics of the filter suface. IV-1200 and Nutrivex filters showed a higher and more stable filtration rate than the other 1.2 μm filters. The concentration and the average particle diameter and distribution of fat emulsion were not affected by the filtration through any of the filters examined. In conclusion, the fat emulsion could befiltered with 1.2 μmfilters solely by gravity and its phannaceutical stability was also sufficiently maintained during the filtration.

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We studied the compatibility in mixing any two of eight kinds of ophthalmic solutions which are frequently used in operations for glaucoma or cataract.
Changes in the appearance, pH value, osmotic pressure and viscosity were checked immediately after mixing, both 1 hour and 24 hours after mixing and keeping in a dark place at room temperature. In some combinations, the mixture became turbid probably due to some of antiseptics to other ingredients. Regarding Noflo Ophthalmic Solution, white needle crystals were generated when mixed with some other drugs. These crystals were identified as norfloxacin (a principal ingredient of Noflo Ophthalmic Solution) by high-performance liquid chromatography and were found to be formed by the increase of pH. From these results, close attention should be paid to the order and intervals in the successive administration of various many ophthalmic solutions while taking into account not only any incompatibility of the antiseptics as well as any changes in the pH values.

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We developed a computerized provision system for the instruction of medication to patients. This on-line system was developed as a partof the total dispensing support system on the dispensing room LAN which was linked with prescription order entry system. Drug information such as identification guide (drug form, cord number), indications or efficacy, and side-effects, was inputted to drug master files of the dispensing support system. The medication history for each patient, including the initial consultations, subsequent consultations and multiple clinical department consultation was cited from the database file that was constructed in the dispensing support system. When the physician prescribed a drug for a patient, the drug information and medication history were printed out on patient medication instruction sheet and previous were printed on prescription check-list by the drug envelope printer concurrently with the prescription. The patient medication instruction sheet informed patients about their medicine-what kind of medicine; how to take it effectively; what possible side-effects might occur and what to do about them; and any other special instructions, -which were written in clear and understandable terms for the patient. The prescription and the prescription check-list informed pharmacists about the patients-who had been prescribed newly; whose prescriptions had been altered from previous; who consulted multiple clinical departments and so on. These information are necessary for pharmacist to instruct patients.
This on-line system enabled pharmacists to provide instruction of medication to patients not only “in written form” but also “in oral form” . We therefore, consider this system to be useful for the rational use of medication.

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We developed a software program with the aid of a personal computer, which enables the preparation of information sheets regarding drugs prescribed for out-patients by using a commercially available software package (FileMaker Pro). Guest computers can use this program simultaneously if they are connected with TCP/IP through a local area network (LAN). The program consists of two databases: one is for the drugs kept in the pharmacy (drug database) and the other is for the drugs prescribed for individual patients (patient database). The former contains information such as the name, color image, actions, usage, dosage, precautions and the main side eftects of each drug. Using a relational function with FileMaker Pro software enables the user to transfer drug information data automatically into the patient database. Data on any drug can be directly obtained from the drug database into the patient database on an information sheet by inputting the first three letters of the drug's name. This rapidly provides full information about not only the mechanism of action of any drug, but also about any possible side effects and drugs prescribed by another hospital.

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Mistakes in filling prescriptions at outside pharmacies can sometimes lead to hospitalization, especially in the case of children. To counter this problem, we began to issue a “drug-record poketbook” to provide information to pharmacies and to educate the parents. We developed a system for drug management guidance in pediatrics aimed at improving the quality of guidance for medication. This system makes use of TDM, allows the participation in doctors' rounds, and provides pamphlets explaining certain points that the potients need to be careful about. After the introduction of this system, the number of dispensing errors at pharmacies decreased. This comprehensive information system enabled the monitoring of both inpatients as well as outpatients. These results show this system is a useful contribution to the service for patients.

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A computer system for delivering drug information leaflets for patients has been introduced at Hokkaido University Hospital. This system can print out the trade name, color picture, dosage and administration, efficacies, symptoms of side effects, and directions at the time of taking medicine can store about 1, 400 items. The information regarding the efficacies and symptoms of side effects was carefully reviewed beforehand by medical doctors. These information leaflets are now provided to out-patients under instructions from medical doctors.
Evidence thus far suggests that these leaflets produce a favorable impression on patients for a safety and a proper use of medicines.

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