New hydrogel patches (PL patches) containing local anesthetics were developed. The percutaneous absorption and usefulness of the PL patches prepared with water-soluble dietary fibers, xanthan and locust bean gums, containing an eutectic mixture of prilocaine and lidocaine were investigated. The evaluation of percutaneous absorption and topical anesthetic efficacy were respectively performed by the measurement of drug concentrations in hairless rat skin and the Pin-Prick method with normal healthy volunteers. The drug concentrations in hairless rat skin greatly increased with the additives such as ethanol and l-menthol. The amount of absorbed drugs was in proportion to the increase of ethanol concentration. Adjusting purified water at pH 9.0 in the preparation of PL patches seems to be an important factor in promoting absorption of the eutectic mixture. The effect of application time suggested that the apparent absorption rate of the PL patches containing ethanol became larger after 45 min compared with PL cream used as a control. The pain scores determined by the Pin-Prick method indicated that the PL patches both prepared with purified water (adjusted at pH 9.0) containing ethanol (20%(v/v)) and including ethanol (20%(v/v)) with l-menthol (1%(w/v)) were significantly more effective than the commercial lidocaine tape and PL cream. In a clinical treatment study, the pain accompanying the removal of molluscum contagiosum was successfully blocked by the application of the PL patches. These results suggested that the PL patches prepared with water-soluble dietary fibers containing an eutectic mixture were quite useful as practical local anesthetic preparations.

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Six kinds of well-prescribed admixtures of commercially available ointments and/or creams were selected from the prescribed sheets in our hospital. The skin permeability of corticosteroid from these admixtures was investigated by in vitro experiments using hairless mice skin. The permeability of corticosteroid through skin after adaptation of corticosteroid creams (Lidomex^®) alone was approximately 9-fold larger as compared with that of the ointments only.The pemeability of conicosteroid in the admixture of Nedsona Universal^®cream or Lidomex^®ointment and urea ointments respectively was 3-and 5-fold larger than that from the cream and ointments alone. However, urea ointments did not influence the permeability of the drug in Lidomex^®creams.This suggested that the w/o-type urea ointments more greatly enhanced the permeability of corticosteroid as compared with the o/w type urea ointments. The extent of the stability of the emulsion after mixing was related to the permeability. These results suggest that admixing ointments and/or creams should be carried done among bases having similar physicochemical characteristics.

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Characterization of powdered drugs depends on a visual inspection of the dispenser in most hospitals. And one of the most important problems of visual inspection is its lack of reliance that must be excluded from the actual preparation of the drug itself.
In this study, we attempted to develop a method to resolve this problem using a quick and easy procedure presenting greater reliability than the currently applied visual one.
Combining non-solvent sample preparation, opal glass absorption spectroscopy, baseline collection, the relative strengths of absorbance at three wavelengths (Qr values), and a computer system, we developed a method by which characterization of drugs can be done quickly and easily, even if the subject mixture contains 2-3 kinds of drugs.
Characterization of drugs using the method has one principal defect, however, that it demands Qr values of pure components before use, unless the characteriation of drugs can not be accomplished from the Qr plot.
In spite of this fault, the Qr plot prepared by the method is useful for the characterization of drugs in a hospital pharmacy because even the calculation of the Qr plot is sufficient to demonstrate to the operator whether or not the preparation is correct.

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A simplified procedure was developed for the determination of granisetron (GRN), a selective 5-HT₃ receptor antagonist, in human plasma by high-performance liquid chromatography. The procedure involves elution of GRN from plasma by solid-phase extraction prior to reversed-phase chromatographic separation on a cyano propyl silica column with subsequent quantification with a fluorescence detector. Using 1 ml of plasma sample, linear responses in concentration-peak area ratios were observed to range from 0.1 to 25.0ng/ml plasma. The coefficient of variance value of the measurement was below 5% across the calibration range, and the recovery of GRN from plasma reached 98%. The assay method was applied to determine the plasma level of GRN in healthy adults after a single oral administration (2mg), followed by analysis according to a 2-compartment open model employing first-order absorption. This method was found to be useful to support drug monitoring and pharmacokinetic studies for GRN.

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We discuss the correlation between plasma concentration and clinical dose of Clonazepam (CZP) combined with other anticonvulsants in epileptic children. The plasma concentrations were measured in 610 samples from 141 children (73 males and 68 females) by HPLC method. We found that the clinical doses of CZP in our hospital were lower than those directed in “Goodman and Gilman's The Pharmacological Basis of Therapeutics” and in “United States Pharmacopoeia Dispensing Information”, and that therefore the plasma concentrations were distributed at the low range correspondingly with doses. A correlation between plasma concentration and clinical doses of CZP was observed and the relationship depended on sex and age of the patients. The plasma concentration of CZP in the older group (over 11 years old) was higher than that in the younger group (from 0 to 10 years old) and that in the male group was higher than that in the female group.
We surveyed the relationship between the plasma concentration and dose of CZP in two patients over the longterm. The results indicated the necessity for frequent therapeutic drug monitoring of CZP over the longterm at the changes of dose and patient weight.

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A midazolam lollipop was prepared to improve the QOL of pediatric patients given premedication and to expect absorption of midazolam from oral mucosa.
A mixture of sucrose, glutinous starch syrup and orange flavor was employed to prepare the midazolam lollipop for masking the bitter taste of midazolam.
In the quality test, the coefficient of variation of midazolam concentration in the lollipop ranged from 1.81 to 6.53 CV%.
In the clinical examination, 50 patients, aged 6 months to 6 years old, were recruited. Children weighing under 15 kg were given one lollipop and over 15 kg were given two at 30 minutes before entering the operating room. 42 patients were willing to accept the midazolam lollipop and we consequently obtained the sedate condition satisfactorily at the induction of anesthesia.
In conclusion, the midazolam lollipop may constitute a more effective dosage form as a premedicant for pedriatric patients than previous forms and it may be less disturbing mentally and physically because most children like lollipops.

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Changes in the serum level of four antiepileptics (phenytoin, phenobarbital, carbamazepine, and valproic acid), which were measured by Okayama University Medical School Hospital, were surveyed for 14 years from 1981. The distribution of phenytoin concentrations in serum shifted from a low-concentration area to a wide-ranging area. The phenobarbital concentrations were distributed from wide-ranging area to a low-concentration area and recently again to a wide-ranging area. The distribution of carbamazepine concentration changed from a low-concentration area to a middle-ranging area. The distribution of valproic acid concentration altered from a low-concentration area to a wide-ranging area containing a very high-concentration area. In analyzing the distribution of each drug concerning its effective therapeutic concentration, phenytoin and phenobarbital presented low ratios, whereas the ratios of valproic acid and carbamazepine were very high. These results suggest that the direction of the serum level of these four measured antiepileptic drugs differed. They also suggested that serum level monitoring of antiepileptic drug is useful for administering the drug therapy of epileptic patients.

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We analyzed the method for oral administration of antiepileptic drugs in 50 child epileptic patients, who were given medication instruction during hospitalization at the Department of Child Neurology for 10 months from October 1, 1993 to the end of July 1994. The average age of patients was 6.2 (0-17) years old. Sodium valproate (VPA) was the highest rate (70%) in the antiepileptic drugs prescribed. A total of 154 different dosage forms were used in 50 patients, and the average use was 3.1. The ratio of powders, tablets, solutions and suppositories in prescribed dosage form were 70, 14, 12 and 4%, respectively. Analysis of the method by which the powdered drugs were administered with “water or Japanese tea”, “dissolved powdered milk or fresh cows milk”, “juices” and “any other means” revealed a ratio of 58, 17, 17 and 8%, respectively. In the medication instruction, the familyies of the younger-aged patients were queried as to the taste of drugs, method for taking medicine, and interactions with the drink. The results derived suggest the possibility that the analysis of problems concerning the dosage form and taste of antiepileptic drugs contribute to improving the patients' quality of life when their epilepsy is treated. Thus, the research and development of a new antiepileptic dosage form are necessary to solve these problems.

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The actual state of re-examination of the pharmacist's fee claim forms is unsufficiently understood for both medical care institutions and insurance-pharmacies. Accordingly we analyzed contents of 881 among 1440 cases which had been actually re-examined by the National Health Insurance Examination Committee of Medical Fees in Fukushima Prefecture in January 1996.
Three-fourths of assessment cases corresponded to one of the official reasons, “Not indication” . Pharmacists in the medical care institutions should examine the actual plan for contribution to appropriate legal prescription delivery. Moreover it is impossible for insurance-pharmacies to assess pharmaceutical management and counseling service when the patient's disese is unclear. It is thus necessary to construct the system based on the patient's information being mutually available to medical care institutions and insurance pharmacies.

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Intrahospital sterile preparation of multiple admixtures of injectates and intravenous hyperalimentation (IVH) by pharmacists is now becoming an accepted practice. There appeared to be no software for Macintosh, at least on a publication basis, for calculating nutritional components in the parenteral solutions, while there were some for NEC computers. We therefore developed a nutrition management program of injections (named “MacMEQ” ) under HyperCard on Macintosh personal computers, which cannot only perform the nutritional calculation but can also search solutions under adequate nutritional conditions and find inappropriate combinations of multiple mixtures. This has led to the expectation that, by utilizing MacMEQ, pharmacists can efficiently manage nutritional information of parenteral solutions to ensure the safety of patients.

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We have converted our hospital information system used in Hamamatsu University School of Medicine from a host on-line system to a client-server system (PC-ordering). Problems and efficiencies in the use of this new order entry system for prescriptions were subsequently evaluated.
Several merits were identified such as contraindicational drug use, drug interaction and duplication checking systems, but many problems still remain to be overcome in the PCordering system package produced by NEC.
We classified these problems into three categories:(1) data transfer problems, (2) system conversion problems, and (3) client-server system problems.

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We developed a new method for preparing a diluted aseptic solutipn of benzalkonium chloride (BAC) using a commercially available plastic bottle of sterile distilled water for injection. A rubber patch was attached to the shoulder of the plastic bottle immediately after the sterilization had been done using 70% ethanol. A solution containing 10% BAC filtered through a membrane with a mean pore size of 0.22μm was injected into the plastic bottle through the rubber patch: In order to assess the aseptic lezel of the solution prepared according to this method, we aseptically filled the bottle with two culture media consisting of soybean casein digest broth (n=20) or glucose peptone broth (n=20). Tap water was also injected into the bottle according to the procedure. Each of these resulted in a negative bacterial contamination. No change was observed in the BAC contents, pH values and bactericidal activities against five strains (S. aureus, E. coli, P. aeruginosa, S. marcescens, and F. meningosepticum) of the BAC solutions (0.02% and 0.1%) tested during the storage period of six months at room temperature. The time required for preparing a solution by this method was about one-fifth of that according by the preestablished method where a grass bottle containing a diluted disinfectant solution was sterilized using an autoclave.

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Prescription drug-nonprescription drug interactions represent a substantial problem that may result in adverse side-effects or toxicity in pharmacy practice. We constructed a database of simultaneous-use and drug-interaction information between switch-OTC-drugs and prescription drugs. This database is laid out by using “the CARD for windows” software currently available on the market. Our database included information on 1, 235 simultaneous-use and 169 drug-interactions. To fulfill the pharmacist's role as advisor on health care, this database offers the advantages of ease of use and quick accessibility.

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