The correlation between the digoxin elixir dosage and the serum digoxin concentration was examined 230 serum samples obtained from 159 children (67 males and 92 females, ranging in age from 0 to 10 years old) receiving digoxin elixir. An average maintenance dose for infants under 4 months old was 0.008 mg/kg/day, and was 0.01 mg/kg/day for children aged 4 months to 10 years old. The average serum digoxin concentration in these children was 2.03 ng/ml in neonates under 1 month old, 1.33 ng/ml in 1 to 4-month-old infants, 0.9 ng/ml in 4-month-to 2-year-old children, 0.86 ng/ml in 2-to 6-year-old children, and 0.73 ng/ml in 6-to 10-year-old children. Although the dosage used for infants under 4 months old was below that stipulated in writing in the product information (0.012-0.027 mg/kg, under 2 years old), the serum digoxin concentration of infants under 1 month old was 2.03 ng/ml, which was significantly high. And in the pther cases, considerable variation was observed between the dosage per body weight and the serum digoxin concentration in each age.
These findings suggest that it is necessary to reconsider the dosage written in the product information. Particularly, in infants, the variation of serum digoxin concentration in the individual patients was great even if in the same dosage. Therefore, fixing the dosage is desirable by carefully monitoring the serum digoxin concentration in each patient.

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Two types of mefenamic acid (MA) suppositories were prepared, one with Vosco^®, an oleaginous base (Vosco suppository) and another with polyethylene glycol (PEG), a watersoluble base (PEG suppository). The crystallinities of MA in the Vosco and PEG suppositories, the in vitro release behaviors of MA from them, and the pharmacokinetics of MA following their rectal administarations to healthy volunteers were respectively compared. X-ray diffractometry revealed that MA in the Vosco suppository was mainly dispersed in a crystal form, whereas MA in the PEG suppository was disseminated in the amorphous state, with the in vitro release of MA from the PEG suppository being faster. MA in the Vosco or PEG suppository was chemically stable, and the in vitro release behavior of MA from each suppository did not change after storage for 2 months at 5°C. The serum MA maximum concentration (C_max) and the time to reach C_max after rectal administration of the PEG suppository appeared to be respectively higher and to be shorter than those of the Vosco suppository. The areas under the serum MA concentration-time curves (AUCs) from zero time to 8 h for the Vosco and PEG suppositories were 3.2 and 4.1 μg·h/ml, respectively, and their values were not significantly different. It was concluded that the PEG suppository presented a faster release characteristic of MA than did the Vosco suppository and that the serum MA concentration profiles arising after administration of these suppositories reflected their release characteristics.

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The clinical pharmacokinetics of disopyramide (DP) were studied after single oral adminis tration of 200, 300 or 350 mg to healthy subjects and patients suffering from arrhythmia. The mean peak concentration of DP in serum (Cmax) was 3.98μg/ml, observed at a mean of 1.65h (tmax) after oral administration of 300 mg in the healthy subjects, and was 2.96μg/ml at 2.65h in the patients. The elimination rate constant (kel) and oral clearance (Cl/F) in the patients were significantly lower than those in the healthy subjects (0.144h^-1 vs. 0.099h^-1 for kel (p<0.05) and 9.11l/h vs. 6.14l/h for Cl/ F (p<0.05), respectively). Oral clearance was significantly correlated with creatinine clearance in the patients.
DP treatment was effective in three of four patients suffering from premature ventricular contractions and in all four patients suffering from premature atrial contractions, in whom the effective level of DP was 1.4μg/ml. DP treatment was also effective in four of nine patients suffering from atrial fibrillation, in whom the effective level of DP was more than 1.9μg/ml. However, the minimum effective level of DP varied widely among the patients, thus necessitating monitoring of the serum DP concentration for effective treatment of arrhythmia.

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Serum levels of the nadolol stereoisomers, racemate A and B, in man were determined by high-performance liquid chromatography using a fluorescence detector following single oral administration at a dose of 60mg. The mean serum levels of racemate A and B were maximal 3.6h after dosings of nadonol racemate A and B with levels of 23.6 and 22.5ng/ml, respectively, followed by a biphasic decrease with apparent terminal elimination half-lives of 19.7 and 16.5h, respectively. Paired statistically significiant differences were found for serum levels, elimination of half-lives and the area under the curve following the nadolol dosing of racemate A and B. An average of 28.4% and 23.6% of racemate A and B were respectively bound to serum protein, suggesting that serum levels and elimination of the half-lives of racemate A and B were different. Also, significant differences were found for serum levels of racemate A and B after constant administration of 30mg of nadolol per day in 17 patients.

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We investigated the enzymatic mechanisms of resistance to antibiotics and the profiles of plasmid DNA in ampicillin-resitant Staphylococcus aureus (10 strains) isolated from clinical materials.β-Lactamase activity was determined using the acidmetric disk method; the PCase (penicillinase) activity was observed in all except one strain tested, whereas no CSase (cephalo sporinase) activity was noted. All of the strains tested were susceptible in vitro to AMK, MINO and VAN, but were resistant to β-lactam atibiotics. Antibacterial activity of AMK against all of the strains tested was less than 6.25μg/ml (MIC) and that of GM was more than 12.5μg/ml.
Compared to the profiles of plasmid DNA derived by the electrophoresis pattern, the strains tested can be classified into two groups: Group I (6 strains) produced two plasmid DNA patterns obtained from plasmid DNA larger than the 23 kbase and around the 564 base, and Group II (4 strains) produced a different patter to those of Group I. These findings indicate thatDNA plasmid larger than 23 dbase in ARSA is thought to be affect the resistance against β-lactam and aminoglycoside antibiotics, such as through modification of the chemical structure.

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Unclaimed prescriptions directly increase the number of non-compliance patients. A survey of drug inventories was conducted prior to and following implementation of outpatient prescription ordering to determine how such ordering affects stocks of unclaimed patient-subscribed medications. Results showed that while the institution of ordering tends to increase the incidence of unclaimed prescriptions, measures can be taken to reduce these stockpiles. It was also found that, after ordering had been implemented, many patients were unaware that prescriptions had been issued. It is therefore necessary to create some sort of system enabling patients to check on prescriptions at any time.

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We investigated the mechanism of isosorbide dinitrate (ISDN) loss from solution to the Ethylene-vinylacetate (EVA) copolymer container. When the parenteral injection diluted with isotonic sodium chloride solution was stored in the EVA container, the ISDN concentration was reduced to 92.1% in 24 h. A linear relation was observed between the amount of ISDN sorbed to the EVA membrane and the equilibrium concentration of the diluted solution within the 5-200μg/ml range. The results suggest that the ISDN loss from the solution occurred through the mechanism of partition and diffusion to the EVA membrane.

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Compatibility of sustained-released fine granules of nifedipine (SRN) with 21 kinds of drug were studied. The mixtures of SRN and drugs in heat-sealed packages (polyethylene-laminated glassine paper) were kept at 20°C and 75% relative humidity (R. H.) or 30°C and 92% R. H. for 30 days. Weight change and color of samples were recorded. Dissolution tests of nifedipine from the mixtures of SRN and the drugs were studied in J. P. disintegration media No.1 and No.2. Significant incompatibility was not observed in the weight change, nor was significant change of dissolution of nifedipine noted except for the combination with sodium bicarbonate. Dissolution of nifedipine was enhanced by sodium bicarbonate in disintegration medium No.1.
We further studied photodegradation of nifedipine in SRN. Fluorescent light was irradiated (1000 lx) on SRN in a petridish wrapped with polyvinylidenchloride film, in a heat-sealed package, in a heat-sealed package kept in a paper bag, and in a heat-sealed package kept in a light-resistant multi-layered laminate bag. Except for the light-resistant bag, light irradiation produced considerable unstability in nifedipine in SRN.

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The regulations formulated in the past 10 years for morphine preparations at Fukushima Medical College Hospital are described. The amount of morphine preparations, which were returned and reused, increased in parallel with the number of prescriptions for morphine preparations. In contrast, the volume of morphine preparations disposed dramatically decreased during the past 2 years. During the past 10 years, no problems arose concerning the regulations for morphine preparations.

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The frequency of prescriptions given for various antihypertensive drugs (namely, calcium antagonists, beta-blocking drugs, diuretics, angiotension-converting enzyme inhibitors (ACEI), and alpha-antagonists) for outpatients with hypertension was studied for 1992, and compared with that for 1990 and 1988. In 1988, prescription of calcium antagonists was made most frequently, and further increased in 1990 and again in 1992. Prescription of diuretics decreased and that of ACEI increased in 1990 and again in 1992. The percentage of patients who were medicated by a single drug was 52% in 1988, and further increased in 1990 and again in 1992. Most of the patients were medicated by a single or two drugs in the three periods. In patients medicated by a single drug, prescription of calcium antagonists or ACEI increased in 1992, while that of diuretics decreased in 1992. Patients who received the drug three times a day decreased, and those twice a day increased in 1992. In conclusion, the frequency of the prescription of calcium antagonists and ACEI increased in 1992, and long-acting drugs were more frequently prescribed in the same year.

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We queried by questionnaire the outpatients who were taking inhalant solutions were prepared in our hospital about how they were using these solutions. As the result, we found that it was generally difficult for a patient to handle a nebulizer hygienically. Accordingly, we believe that it is necessary to research the stability of the constituent as well as the microbial contamination after the prepared inhalants are handed to the patients. As the conclusion of ourresearch, we plan to prepare a leaflet that demonstrates how to handle prepared inhalant solutions correctly.

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At Kyoto University Hospital, disinfectants are prepared by injecting the concentrated disinfectant agents directly into 500 ml bottles of sterile purified water, which are equipped with a new open-top screw-cap. When our new disinfectant preparation method using the open-top screw-cap was compared with that using the regular screw-cap, the method was found to be much more useful from a variety of perspectives, such as hermetic sealing, sterilizing, handling and treatment time. In addition, the open-top screw-cap wrapped with a plastic cover seat could easily prevent contamination by a range of bacteria during disinfectant preparation which was considered to be of value in the preparation of disinfectants in hospital pharmacy.

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An automated rate nephelometric assay (Beckman Array 360 System) for phenobarbital (PB) and carbamazepine (CBZ) was evaluated. The assay offers measuring ranges of 5-120μg/ml serum for PB and 2-40μg/ml for CBZ. The coefficients of variation for within-run and between-run precision for both PB and CBZ were< 5.0%. Test results were not significantly affected by bilirubin-unconjugated (up to 19.2 mg/ dl), bilirubin-conjugated (21.3 mg/dl), hemoglobin (540 mg/dl), turbidity (2070 units), or other antiepileptic drugs. The method produced satisfactory results in dilution tests. Quantitative results obtained by the Array 360 assay on serum samples from patients were compared with those obtained by the fluorescence polarization immunoassay (FPIA) and homogeneous enzyme immunoassay (EMIT) methods. The results correlated well with FPIA (r=0.996 and 0.981 for PB and CBZ, respectively) and EMIT (r=0.994 and 0.983). The Array 360 assay was concluded to be an appropriate and quick method for PB and CBZ determination.

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Introducing a barcode system enables systematic inventory control in drug dispensaries and pharmacies. Additionally, the system efficiently reduces the number of personnel and rationalizes the inventory at the same time. In developing this new inventory control system employing barcodes using a microcomputer, we have greatly facilitated rationalizing pharmaceutical storeroom management.

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