Fibronectin (FN) has been reported to be effective for the treatment of corneal trophic ulcers, but the FN eyedrop preparation is not a simple technique. We previously developed an automatic device to prepare FN eyedrops using a patient's own plasma (Yoshida et al. Jpn. J. Hosp. Pharm., 24, 493-498 (1998)). The aim of this study was to evaluate the efficiency of this automatic device. FN eyedrops were prepared using plasma from healthy individuals either with an automatic device or a manual process using gelatin-coupled Sepharose 4 B (GS 4 B) and Sephadex G-25 (PD-10), The average FN concentration and the recovery rate in the eyedrops prepared using the automatic device were 653±57μg per ml and 55±5%, respectively, but those prepared using the manual process were 563±50μg per ml and 46±6%, respectively. The operation of the device was easyand the recovery values of FN were similaramong all operators. The total preparation time of FN eyedrops was approximately 1 hour. This automatic device was thus found to be useful for preparing FN eyedrops from the patient's own plasma.

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Nineteen patients with lung cancer were given a combination treatment of etoposide and carboplatin: the former was administered orally once a day at a dosage of 50 mg/body/day for 21 consecutive days, and the latter was administered intravenously over a period of 1 hour in doses ranging from 300 to 400 mg/m² on day 1. In addition, a pharmacokinetic study of etoposide on day 1 and an assessment of any side effects were performed. These patients were all classified by the experience of gastrectomy. In patients with gastrectomies (n=5), etoposide had to be discontinued after 13-17 days, due to the fact that the side effects such as vomiting, and hematological toxicity in patien ts with gastrectomies were more pronounoed than that of nongastrectomy group (n=14). Forthermore, in patients with gastrectomies, the maximum serum concentration (C_max) of etoposide was significantly higher (p< 0.05) namely about 1.6 times, and the area under the curve from zero to ∞(AUC_0-∞) was also significantly greater (p<0.05) namely about 1.7 times the values for the non-gastrectomy group (n=14).
These observations indicate that the extent of side effects in patients with gastrectomies appears to be correlated with the serum concentration of etoposide. Accordingly, when etoposide is orally administered in patients with gastrectomies, it may thus be necessary to determine the serum concentration of etoposide, as well as carefully monitoring any side effects, and as a result, it may be necessary to reduce the dosage of etoposide.

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The present study examined the pharmacokinetics of anticancer drugs in the cerebrospinal fluid (CSF) during CSF perfusion or injection chemotherapy. A 69-year-old Japanese woman with disseminated glioblastoma received one course of both ventricular-lumbar (V-L) and lumbarventricular (L-V) CSF perfusion chemotherapy, and one course of both ventricular and lumbar injection chemotherapy with methotrexate (MTX), cytosine arabinoside (Ara-C), and nimustine (ACNU). Samples of CSF from the ventricles and lumbar spinal canal were obtained via the Ommaya reservoirs. The drug concentrations in the CSF were measured by either fluorescence polarization immunoassay or high performance liquid chromatography. In the V-L CSF perfusion chemotherapy, the maximum CSF concentrations of the three drugs in the lumbar spinal canal were lower than those in the ventricles. However, the concentrations of MTX and Ara-C in the lumbar spinal canal exceeded those in the ventricles 3 hours after the perfusion. The area under the CSF concentration versus the time curves (AUC) of MTX and Ara-C in the lumbar spinal canal were 175.7 and 76.2%, respectively, of those in the ventricles. In the L-V CSF perfusion chemotherapy, the CSF concentrations of the three drugs in the lumbar spinal canal were higher than those in the ventricle. The AUCs of MTX and Ara-C in the ventricles were 15.5 and 18.4 %, respectively, of those in the lumbar spinal canal. In the ventricular CSF injection, the initial CSF concentrations of the three drugs in the ventricles were higher than those in the lumbar spinal canal. However, the CSF concentrations of MTX and Ara-C in the lumbar spinal canal exceeded those in the ventricles 12 hours after the injection. Although the concentration of ACNU in the ventricles was only detectable at 3 hours after the injection, no concentration in the lumbar spinal canal was detectable. The AUCs of MTX and Ara-C in the lumbar spinal canal were 84.6 and 29.1%, respectively, of those in the ventricles. In the lumbar CSF injection, the CSF concentrations of MTX and Ara-C in the ventricles were detectable but lower than those in the lumbar. Although the CSF concentration of ACNU in the lumbar spinal canal was only detectable at 3 hours after the injection, no concentration in the ventricles was detectable. The AUC of MTX in the ventricles was 0.31% of that in the lumbar spinal canal. These results indicate that CSF perfusion chemotherapy may thus be a more useful treatment than CSF injection chemotherapy to patients with disseminated brain tumors.

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To confirm the stability of tablets and capsules in one-dose packaging dispensation, we studied changes in three different storage conditions regarding the external appearance, weight, hardness, disintegration time and contents.
A change in the external appearance change was observed in two medicines under severe (temperature: 30°C), RH (relative humidity: 75%) one-dose package and naked conditions. Changes were in medicines in which the naked eye could not detect any changes regarding the color for 3 medicines. A weight change was observed in tablets made in one medicine. The hardness of the Lorazepam was found to decline by about 50% in severe conditions. A decline in the disintegration time was seen in Lisuride Maleate after 24 hours with (temperature: 26-32°C, RH: 43-70%). On the other hand, the Same disintesation time increased in severe condition. Change were seen regarding ofthe 5 medicines. A decline of about 50% was observed in Serrapeptase in under severe conditions. Based on the above findings the stability of medicines should therfore be carefully monitored when using one-dose packaging

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As DDS drugs with various drug delivery functions are often prescribed under in conbination with a widerange of concurrent drug therapies, drug information closely related to its clinical usage is required to guarantee the appropriate multiple pharmaceutical functions of DDS drugs: We surveyed the actual concurrent therapy of lipo-PGE₁ (Palux^® inj. and Liple^®), a targeting-type DDS, with various aqueous infusions at both Okayama University Hospital and Fukui Medical School Hospital. The term of the survey, which was done by evaluating the prescription records, and the total number of prescriptions were 14 months and 1, 005 prescriptions, respectively. Lipo-PGE₁ was scarcely administered without any concurrently prescribed infusions. Although lipo-PGE₁ was mostly diluted with Glucose Injection or Isotonic Sodium Chloride Solution, some electrolyte infusions were also concurrently prescribed with Lipo-PGE₁ in some cases. The magnification of the dilution and the administration route seemed to be related each other. The data revealed in this report ave considered to be useful for a clinical usage-based assessment system to obtain further information guaranteeing the drug delivery function of Lipo-PGE₁ from both a pharmaceutical and pharmacodynamic viewpoint one word.

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Recently, automatic tablet counting and packaging machines have come to be widely used for the one-dose packaging of tablets and capsules. However, coloration, i.e. changes in color, of such tablets repackaged by one-dose packaging machins for dispensing has been frequently observed in several kinds of tablets due to the light, humidity and temperature in the room. In this report, the changes observed over time in the controlled-release mesalazine product, Pentasa^® tablets, repackaged with polyethylene-laminated cellophane and glassine films for the one-dose packaging was studied.
The repackaged tablets changed color within a week at room conditions (22-25°C, 50-70% RH) under a 350 lux fluorescent white-1 amp ex posure for 12 h per day or in darkness. However, no coloration was observed for at least four weeks in a refrigerator (4°C, 20% RH) in dark ness. The weight of the repackaged tablets increased by about 1% at room conditions within a week, while no such weight increase in the tablets was observed while the tablets were kept in a refrigerator. No changes in the amounts of mesalazine and its degradates, gentigic acid and p-aminophenol, in the tablets were observed and the dissolution properties of mesalazine from the tablets also remained unchanged during the experimental period.
Based on these findings, we conclude that the one-dose packaging of Pentasa^® tablets is not a suitable procedure since it results in the absorption of moisture and changes in color.

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Coring, which is the name for when a piece of rubber is shaved off from the rubber stopper of a vial when the needle punctures it, is herein reported. We investigated whether or not coring could happen with insulin injections, and also whether or not such pieces of rubber could then actually pass through the needle. Vials for syringes and pen type injectors were used with 29, 30 and 31 gauge (G) needles, under cool and room temperature conditions, and at 60/90 degree puncturing angles. The shapes, sizes and number of pieces of rubber were measured at the 10th and 30 th puncturing times. For the passage test, the presence rubber pieces was measured during air venting, as well as in the insulin liquid actually ejected and in the liquid in the vial.
Coring often occurs in vials for syringes under cool conditions. Vials for pen type injectors also show coring under all the above conditions. The rubber pieces which passed through the needle could be found in both air venting and the insulin liquid. Coring was shown in thin hypodermic syringes, such as 29-31 G, and there was evidence that such rubber pieces may be dangerous if they enter the body. Rubber pieces can pass through the needle in a vial for pen type injectors, due to the design of the fixed needle in the injector. Based on our findings a safer injection system which prevents coring should thus be develepoed.
In addition Careful attention should also be paid to patients with rubber allergies.

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Recently, patients require increasingly more information about prescribed drugs. Many hospitals are thus providing dispensed drug information to outpatients. We surveyed about the present condition of dispensed drug information for outpatients at the 22 municipal hospitals in Osaka prefecture.
As a result, dispensed drug information was provided by 18 of the 22 hospitals. the data used for the dispensed drug information were provided form an order entry system at 9 hospitals, from the receipt data at 3 hospitals, and from the prescription at 6 hospitals. The contents of the information varide regarding side effects and drug interactions.
It is very useful to use data of order entry system or receipt data, but many problems can occur when information is standardized. The development of a flexible system is therefore necessary to solve many such problems. In addition differences in such information between individual hospitals may also cause worry and lead to misunderstandings among patients. We therefore consider it very inportant to unify the contents of the dispensed information.

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Drug-loss in both the dispensing process and the ingestion of powdered-form tacrolimus (PGpowder) was studied, relating the therapeutic drug monitoring of tacrolimus in pediatric patients who have undergones a living-related donor liver transplantation. To simulate drug-loss during the ingestion PG-powder, three ingestion procedures were used ; i. e. a direct ingestion method, and two methods using either a medication-pipette or a medication-cup after suspending the drug with a 10% glucose solution.
The drug-loss resulting from dispensing process was always within 1%. The weight variation of the powders divided by an automatic packaging machine for dispensing was found to be within 4%. The drug-loss resulting from the ingestion procedure was approximately 7% with the direct ingestion method, however, a large loss (ca. 15%) was observed in the case of the medication-cup procedure. This fact suggests that variations in the ingestion procedures therefore affect the blood concentration of tacrolimus.
We thus conclude that a clear understanding of drug-loss in both the dispensing process and ingestion procedure before PG-powder administration is essential in order to perform appropriate therapeutic drug monitoring of tacrolimus to pediatric patients who have difficulty in swallowing capsules.

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We noticed that many gastrointestinal surgery patients who receive TPN therapy tend to show abnormal serum potassium levels. Therefore, to examine the potassium content in ready-made TPN and determine the optimal TPN dose for such patients, we analyzed the patients drug history data using a CP system. As a result, we found controlling the potassium level in patients who have undergone operations for malignant disease, especially in patients with terminal-stage cancer, to be difficult because of the high potassium content in ready-made TPN. It is therefore necessary to design a special prescription regimen which limits the dose of potassium to 1.4mEq /kg or less, especially in patients with terminal stage cancer.

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We noted that terminal stage cancer patients who are continuously administered ready-made hyper-alimentation drip infusions tend to develop metabolic alkalosis while normal serum potassium values. We therefore investigated the medicinal histories of these patients using a computer analysis while also monitoring the drip infusion data to explain this phenomenon.
Consequently we observed that the administration of hyper potassium, furosemide and dexamethasone often results in a decrease in the whole body potassium value in spite of the normal value in the serum finding indicated the occurrence of metabolic alkalosis in terminal stage cancer patients with peritoneal carcinomatosa. Based on these findings, we designed the special menu of intravenous hyper-alimentation drip infusions for patients with peritoneal carcinomatosa.

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We carried out a questionnaire survey at multiple medical institutions to analyze the state of drug side effects in the clinical setting and also studied about the incidence of patients with adverse reactions to drugs, in order to elucidete the symptoms and the causative medicines of such side effects. Moreover, we also investigated how the patients coped with the appearance of the side effects, the proportion of the patients who knew the names of the causative medicine and the sources for any information obtained by them.
This survey was made based on 4264 drug-administered patients who were all mone than 16 years of age from 13 medical institutions, i.e., 9 hospitals and 4 pharmacies in the suburbarn district Niigata City.
The results were as follows:
1. The incidence of the patients with adverse reaction to drugs was 26.9% in total. This incidence decreased with age and was significantly higher in females than in male (ρ<0.001, X²test).
2. Skin disorders were the most common side effect symptom (32.1 %) and the central nervous system drugs were the most frequet (46.7%) causative medicines.
3. The patients who consulted doctors due to adverse drug reactions comprised the largest grovp (74.0%).
4. The proportion of patients who knew the name of the causative medicines was 25.1 %.
5. The patients who had been told the names of the causative medicine by doctors occupied made up the largest group (58.3%) among the patients who demonstrated adverse reaction to drugs.

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In order to investigate the pharmaceutical equivalency of four propentofylline enteric-coated tablets (a pioneer preparation and 3 generic preparations), a quantitative analysis, disintegration testing and dissolution testing were all performed to evaluate them.
The mean contents of propentofylline in each preparation ranged from 96 to 102%. All of the tested materials conformed to the findings for the disintegration test for enteric-coated articles in the thirteeth revised edition of Japanese Pharmacopoeia (JP). However, at the end of the disintegration test with the 1st test medium (pH 1.2), swelling was observed in one or more of the 6 tested tablets for two of the generic preparations. Although no release of propentofylline was recognized, the core of the swollen tablets had completely disintegrated inside the enteric coating film in one of the two swollen generic preparations. When doing the same test aften placing the disks in gastric fluid, the propentofylline finally dissolved in the medium after 120 min. The dissolution test was performed with a paddle (100 rpm) according to JP using a 0.05 M phosphate buffer at pHs of 6.5 and 7.2. The dissolutions were complete in less than 60 min at both pHs, and they were faster at pH 7.2 for all preparations. However, the dissolution was significantly delayed, and the 75% dissolution time was also significantly prolonged for one of the three generic preparations at both pHs when compared to the other preparations.
All of the propentofylline enteric-coated preparations were acceptable based on the JP criteria, however, the pharmaceutical equivalency of the generic preparations to the pioneer preparation heve not yet been obtained. As a result, the changes between generic preparations and pioneer preparations are therefore considered to be considerable, especially ragarding enteric coated preparations

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Since the revision of the Pharmacist Law in Japan, pharmacists must provide patients with informations regarding all dispensed drugs. However, several problems have recently been reported reganding such drug information. A large number of problems are related to discrepancies between the in formation provided by doctors and pharmacists. Therefore, we must direct our attention to these problems in order to solve this dilemma. In the present study, we send a questionnaire to 255 doctors in Hirosaki University Hospital to obtain their opinions regarding the drug information for outpatients provided pharmacists. The questionnaires included 15 questions about the drug information service, and multiple choice questions were used. Completed questionnaires were obtained from 168 doctors (a recovery rate of 65.9%). Forty-five point two percent of the doctors agreed with the drug information provided to the outpatients by pharmacists and 42.9% of doctors agreed with some reservatians. Only 0.6% of the doctors were against this service by pharmacists. Our findings suggest that a large number of doctors would like to know exactly what kind of drug information is provided to the outpatiens by pharmacists. Therefore, they thought it important for pharmacists to closely confer with doctors before dispensing any information, since they would like to give their approval to any such information. The fundamental information of drugs such as the manner and appropriate amounts any dangers of such drug treatment are also required by doctors. The doctors thought that the patients should be informed of any severe adverse events of drugs and drug interactions. On the other hand, 27.3% of doctors did not want to offer, patients any exaggerated information of adverse events and name and/ or effects of anti-cancer drugs. Ten percent of the doctors had gotten into trouble due to information dispensed by pharmacists. However, over 88% of the docters agreed with the work of the drug information service. However, they had misgivings about contradictions regarding the drug information between that given by doctors and pharmacists. If move opportunities for doctors and pharmacists to communicate could be established, then the drug information provided to outpatients would thus be even more useful.

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To investigate the use state of the enteral nutrients, we used in the database of the software program “Resipos Ver.1” for both regimen registration and retrieval, and analyzed the regiments is recipe having been issued by hospital of the Okinawa prefecture in 11 facilities.
As a result, enteral nutrients were found to be most frequently prescribed in the internal medicine department, followed by surgery department, and about 80% of all such cases are prescribed by there two departments.
Regarding the age distribution of the patients for whom enteral nutrient are prescribed, 56% of the patient was older than 65 years old. As a result large amount of enteral nutrients were found to be prescribed for elderly patients.
In addition, ENSURE LIQUID was frequently used as a kind of the medicine and it accounted for about 53% of the all cases using enteral nutrients.
Consequently, enteral nutrients with similar characteristics, components, are frequently prescribed.

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