We investigated the photo-stability of some third-generation cephalosporins in aqueous solution containing such vitamins, as vitamin B₁, B₂, B₆, C, K₂, and panthenol. Although cephem derivatives are stable in aqueous solution without vitamins during 4 hours of sun light irradiation at room temperature, sun light irradiation for 2 hrs did cause the photodegradation of cefotaxime (CTX) in aqueous solution (2 mg/ml) containing flavin adenine dinucleotide (FAD, VB₂ derivative) or pyridoxal phosphate (PAL-P, VB₆ derivative), while, in addition, the residual rate of CTX in the solution also decreased to less than 70%. Similarly, the residual rate of CTX in a solution of benzophenon, a triplet photosensitizer, also rapidly decreased during sun light irradiation. Sun light irradiation also decreased the residual rates of other cephalosporins with an oxyimino group at position 7 under the same conditions.
The main degradation product was identified as an anti-isomer of CTX.
These above described findings thus suggest that FAD and PAL-P may act as photosensitizers in the sun light-induced degradation of cephalosporins.

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We have already demonstrated that 2% aspirin oral ointment is useful for painful diseases of the oral mucosa, however, the aspirin in the ointment degradates gradually at room temperature. In this study, we investigated the efficiency of the stable salicylic acid derivative ethenzamide, as an agent for such oral ointment.
The consistency, spreadability and stability of 2% ethenzamide oral ointment, which was kept at 5°C, 20°C and 30°C, were determined by penetrometer, spreadmeter and HPLC, respectively.
we also investigated its antinociceptive effect based on the Randall-Selitto paw pressure test in rats, and then compared the findings with the effect of aspirin ointment.
In addition eight patients suffering from oral mucous diseases were treated with this 2% ethenzamide oral ointment, and then the clinical effects of the two ointments were compared.
These experiments indicated that 2% ethenzamide oral ointment was more stable than aspirin oral ointment, however, no significant difference was observed between them except for stability. Therefore, on account of its stability, 2% ethenzamide oral ointment is thes considered to be more effective than aspirin ointment in the treatment oral mucosal diseases.

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Beclomethasone dipropionate is a synthetic adrenal cortex hormone that is used in aerosols for the treatment of nasal-allergies. Recently, Aldecin AQ Nasal^® (AQ) has been put on the market as an alternative to Aldecin^® (AD) in which chlorofluorocarbon is used as the propellant. In this study, the spraying characteristics of AQ and AD were examined.
The amount sprayed in one puff with AQ vemain constant from the 7 th to 110 th spray, while that with AD was remained constant from the first to 120 th spray. Therefore, a patient should be requested to spray the AQ at least 7 times prior to the first usage. When the patient spray AQ or AD 4 times a day in both nostrils, then AQ and AD can be for about 14 days and 15 days, respectively.
After the spray tests using different lengths of cylinders and filter paper, a fractal analysis was performed on the sprayed morphology drawn on the filter paper. At a suitable distance from the nozzle of AQ the dispersed particles uniformly settled.
The principal agent was concentrated on the nasal cavity near by the nostrils when the spray test was done by using a plastic nasal cavity model.
This findings suggests that pharmacists must give properly advise patients on how to use AQ while breathing gently.

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To determine benzodiazepines in the serum of patients with acute benzodiazepine (BZD) poisoning, a Fluorescence polarization immunoassay (FPIA) on Abbott's TDx analyzer system was performed. The serum BZD (Flunitrazepam, Etizolam, Clotiazepam) concentrations were measured using benzodiazepine serum reagents. The precision of these assays was determined using three control serums containing 75, 300 and 700 ng/ml of Nordiazepam, respectively. The serums containing 100-2000 ng/ml of BZD were measured by means of FPIA. The relationship between the BZD concentration added and the concentration detected by TDx led us to make two different nomograms depending on the detected range. The FPIA results were compared with the high-performance liquid chromatographic results. There was a close correlation between both findings. The FPIA results and the nomograms were thus considered to be useful in the determination of BZD in the serum. In addition, the rapid determination of the serum in patients with acute BZD poisoning was helpful for confirming the clinical diagnosis for selecting the appropriate treatment.

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In order to evaluate possible changes in the prescribed drugs for injection, the amount of money spent for drugs at Kumamoto University Hospital over the past 9 years was investigated. As a result, some changes were identified regarding the types of drugs used and the amount of money spent. The amounts of money spent for purchasing a group of antibiotics which had been previous representative of frequently used drugs decreased dramatically. On the other hand, the use of plasma preparations, albumins and immunoglobulins etc. have remained stable, except for antithrombin III preparation. In contrast, the amounts of money spent on granulocyte-colony stimulating factors, serotonin receptor antagonist type antiemetics, interferons and nonionic contrast media have increased remarkably. The frequency of prescribing morphine preparartions also tended to increase over the past several years. Based on the present findings, the prescribing of drugs for injection is expected to proceed in a rational and patient-oriented direction from now on.

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The pharmaceutical properties of four vehicles (potato starch, AS; fine lactose, SL; the mixture of the same amounts of AS and SL, AL; extra fine crystalline lactose, EFC) on their mixing ability with antiepileptic drugs (sodium valproate, Depaken^®; clonazepam, Rivotoril^®; carbamazepine, Tegretol^®; phenytoin, Aleviatin^®), as well as on their physical properties and operativeness were examined. Angle of repose of AL, AS, SL and EFC was 53°, 45°, 47° and 44°, respectively. The escapabilities of the four vehicles were 30% or less. The required dividing time for EFC, AL, SL and AS was 53, 96, 217 and 1620 seconds, respectively, and significant differences were also found between each vehicle. In the deviation test, EFC showed a significantly lower variation compared with the other vehicles. In an assay study using HPLC after being mixed with each vehicle, no difference was observed in the contents between clonazepam, carbamazepine and phenytoin, however, EFC, and no others, indicated a lower variation in the mixing content with sodium valproate. There was no difference in the hygroscopicity between each vehicle. These results suggest that EFC is a more efficient vehicle than the other tested vehicles, however, AL, which is used at our hospital, is also considered to be useful as a vehicle.

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In the department of hospital pharmacy of Okayama University Hospital, measurement of serum level of antiepileptic drugs has been conducted since July 1981. We thus surveyed the changes in the number of antiepileptic drugs prescribed over the past 14 years in order to measure the serum concentration. No characteristic change was observed in the age distribution of the patients. The annual number of serum samples and the assay order has gradually increased since 1981. However, the annual number of drug assays per sample were decreased. The frequency of a phenobarbital assay decreased, while the frequency of a valproic acid assay increased. Prescription containing more than 3 drugs decreased while those with only one drug increased. Phenobarbital in monopharmacy therapy shifted to valproic acid. In polypharmacy therapy, phenytoin was mainly prescribed. In polypharmacy therapy, the prescription rate of phenobarbital or primidone decreased, while the rate of valproic acid or carbamazepine increased. Moreover, an increase in various combinations of antiepions of antiepileptic drugs was observed in polypharmacy therapy. Based on these findings, it was suggested that the pharmacological therapy for epilepsy had thus changed from polypharmacy therapy to monopharmacy therapy, mainly due to the increased use of valproic acid.

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Theophylline pharmacokintics at night were evaluated in 20 mild to moderate asthmatic inpatients aged 63.9±13.2 yr (mean±SD) who had been administered a once-a-day theophylline preparation “Uniphyl Tablet” while the serum theophylline concentration was predicted using a pharmacokinetic analysis program designed exclusively for this preparation. The patients were administered the drug daily at 18: 00 pm after dinner. Fourteen patients received a multiple dose (steady state) while six received a single dose. Blood samples to determine the serum theophylline concentration were drawn at 0 (immediately before drug administraton), and at 3, 6, 9, 12 and 15 hours after administration. Tmax was 9.6±2.4 at a steady state and 9.0±2.47 hr at a single dose state, respectively. These findings thus suggest the most suitable time of administration of this preparation to be at from 18: 00 to 20: 00 pm after dinner. In addition, little differnce was observed between the predictive value and observed one. The confidence of the predictive value at 3: 00 and 6: 00 am was high, however, the predictive value also tended to be over predictive in patients whose theophylline clearance was large.

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We developed a HyperText-based program, named “MacAdvice”, for computer-assisted drug compliance instructions on Macintosh personal computers. MacAdvice is equipped with four major functions which can be operated automatically: 1) the preparation of compliance instruction-sheets displaying drug illustrations, dosage, and pharmacological effects both for patients and healthcare providers, 2) listing the histories of drug prescription, 3) an assessment of drug interactions, and 4) analyzing patient's compatiblity with the prescribed drugs. MacAdvice is expected to be a useful tool for pharmacists in the implementation of effective and rapid drug compliance management.

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The prescription entry system for injectable drugs which runs on the ACOS system 3600 /6 (ORDERIG: NEC Corporation) was newly implemented on Apr.3, 1995 for both inpatients and outpatients of Kanazawa University Hospital. The system has been accepted by both physicians and nurses. A 100% entried prescription rate via the system was achieved within one week after the implementation and this system has continued to run smoothly without any problems up to, now.
The implementation of thus system made the supply of injectable drugs for individual patients possible, but the system still needs to develop a check fuction for prescriptions (especialy regarding imcompatibility).

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The supply of injectable drugs for individual patients using the prescription order entry system was started from Apr. of 1995 at Kanazawa University Hospital. The injectable drugs for individual patient are set up by pharmacists into each compartment of the kart (Ordering Kart: Sakase Corporation), and then are carried by nursing assistants to the respective clinical areas.
The characteristics of this supply method are [1] it is set up by 4 pharmacists on a daily schedule (8: 30 am-3: 30 pm), [2] injectable drugs for emergency are louded in a special compartment of the carrying kart, and [3] are set up for prescription entry by the physicians within 24 hours. As a result, it is thus possible to check the prescription (dosage, route, incompatibility and stability), to reduce the stock of injectable drugs in the ward while, in addition, manpower for both the nursing and medical office personnel can be reduced.

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In order to determine the characterristic use of benzodiazepines for insomniacs amongpsychiatrists and other physicians, we retrospectively investigated the prescriptions for outpatients consulting psychiatry, internal medicine 1 and orthopaedic surgery departments at Nagasaki University Hospital. In the psychiatry department, the rate of prescriptions on an intermediate-term or a long-term effective type was approximately 60%, and combinations with 2 or 3 kinds of benzodiazepines were found in approximately 30% of all prescriptions. In the internal medicine 1 and orthopaedic surgery departments, more than 80 % of the benzodiazepines prescribed were an ultrashort-term or a short-term effective type. Other differences in the use of benzodiazepines for insomniac were also observed for the psychiatry and other clinical departments.

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We investigated the stability of 0.05% chlorhexidine gluconate solution (CHG) and 0.05 % benzalkonium chloride solution (BAC) sterilized by high-pressure steam. When CHG was stored at 70°C and 90°C for 21 days, the residual rate decreased to 64.6% and 21.0%, respectively. When CHG was stored at room temperature (R. T.) for 12 months, the residual rate decreased to 84.7%. CHG stored at R. T. for 6 months was completely effective against Escherichia coli and Candida albicans, but not Staphylococcus aureus by the bacteriological test. On the other hand, BAC was stable at high temperature and under the light, and the initial concentration of BAC was kept unchanged for 12 months at R. T.

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