The determination of prednisolone-hemisuccinate (PSL-HS) and prednisolone (PSL) were performed using high-performance liquid chromatography (HPLC). PSL-HS and PSL were simultaneously extracted and injected onto a silica gel column with a syringe-type minicolumn packed with diatomaceous earth granules. The extraction-injection solvent used was dichloromethane containing 1% ethanol and the mobile phase solvent for HPLC was water-acetic acidmethanol-dichloromethane-n-hexane (0.2: 0.2: 4: 95.6, v/v). PSL-HS and PSL were detected using an ultraviolet detector set at 250 nm. Linear relationships between the amount of sample and peak height were confirmedfrom 0.1 to 100 μg/ml of homogenate of rat rectum and human serum. When an aliquot of 5 μl of sample was introduced to the syringe-type minicolumn, the detection limits of PSL-HS and PSL were as low as 100 ng/ml with each. The method is simple and accurate and is thus applicable to pharmacology and pharmacokinetic studies.

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The relationship between changes in plasma amino acid and histological findings in the process of carbon tetrachloride (CCl₄)-induced liver injury was studied in rats intraperitoneally injected with CCl₄ at 0.2 ml/kg twice a week for 5 weeks. The degree of CCl₄-induced liver injury was evaluated by measuring serum GPT activity, and the correlation between serum GPT activity and histological changes was investigated. In the histopathological study, diffuse centrilobular necrosis, coagulation necrosis, acidophilic, ballooning and fatty degeneration, fibrosis, and the formation of pseudolobule of hepatocytes were observed in the liver after CCl₄ administration. Serum GPT activity was elevated after CCl₄ administration and well-correlated with the histologic score of liver injury (r=0.887, p< 0.01). The coagulation necrosis changes and the pseudolobule formation caused by fibrosis proliferation were marked in the rats showing serum GPT activity of more than 500 unit.
The plasma amino acid concentrations increased in the development process of CCl₄-induced liver injury except for that of branched chain amino acids, which decreased with an increase severity of liver damage. The molar ratio of Val+Ile+Leu/Tyr+Phe (Fischer ratio) decreased in parallel to the increase in severity of liver parenchymal damage. The decrease in the Fischer ratio was correlated with serum GPT (r=-0.800), serum GOT (r=-0.711) and histologic scores (r=-0.851). These results suggest that plasma amino acid imbalance occurs prior to liver cirrhosis induced by severe liver damage, and that serum GPT and GOT activities and the Fischer ratio are closely correlated to the histological findings in the development process of CCl₄-induced liver injury.

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A simple and precise method was established for the simultaneous determination of five selected marker components in the kampo (Chinese herbal medicine) extract preparation “Heii-San” using high-performance liquid chromatography with tetra-n-amylammonium bromide (TAA) as an ion-pair reagent.
The most efficient extraction of the five components in Heii-San was made by treating the material with 50% methanol as an extraction solvent with stirring for 15 min at room temperature. For the separation of the components, hesperidin, 6-gingerol, honokiol, glycyrrhizin and magnolol, an ODS column was used with multi-step gradient elution with 10 mM TAA (H₃PO₄, pH 4.0)-acetonitrile as the mobile phase. The acetonitrile content was linearly increased from 25% to 90%. The five main components were eluted within 50 min without interference from coexisting components. The results reveal that the content of the main components, with the exception of hesperidin in the kampo extract preparation was higher than that in oriental pharmaceutical decoctions previously reported.

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The blood concentrations of cyclosporine-A (CyA) decreased remarkably in a pediatric patient who had been administered CyA combined with dried aluminum hydroxide gel (DALG). The difference in the ratio of the dosage per body weight to the blood concentrations of CyA was remarkable in patients who underwent CyA immunosuppressive therapy either with DALG (n=25) or without DALG (n=21). The ratio was 15.6±8.9 (mean±standard deviation) in patients with DALG and 25.9 ±15.4 in those without DALG. After adding DALG to an in vitro pH 1.2 CyA solution, the solution became turbid and the concentration of CyA in the supernatant decreased by about 20 percent compared to the control without DALG. In rats, the area under the curve (AUC) of CyA with DALG was 17 percent lower than that of CyA alone. These findings indicate that the blood concentrations of CyA are affected by administration with DALG, and that aluminum hydroxide gel decreases the absorption of CyA by adsorption or complex formation.

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Theophylline sustained-release dry syrup (TDR·DS) is reported to be effective for treating children with bronchial asthma. In the present study, we studied the release and dissolution of TDR·DS in water using THEODUR^® as well as the effects of the volume and temperature of the water, and the suspension time of TDR·DS. The suspension of TDR·DS in water accelerated the release and dissolution time of theophylline. The release and dissolution times of TDR·DS at 37°C were shorter than those at 20°C. In conclusion, it is better to administer TDR·DS without suspending it in water.

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The plasma carvedilol concentration was significantly lower that the control 0.25 and 0.5 hours after simultaneous administration of carvedilol and talipexole, but was significantly higher at 2. 3. 4 and 8 hours after administration. The drug pharmacokinetic parameters time to C_max (T_max) and elimination half-life (T_1/2) were 4 and 2.8 time higher, after simultaneous administration with talipexole. Also, the area under the concentration-time curve to 24 hours (AUC_0→24) was 2.0 times higher than the control. These changes are thought to be caused by the delay in absorption of carvedilol and metabolic inhibition by talipexol.

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We have reviewed the Japanese literature on patients mistakenly ingesting the plastic press through packages (PTP) together with the tablets or capsules, surveyed the current situation at Kitasato University East Hospital and Kitasato University Hospital (our hospital), and discuss preventive measures.
The literature during the past 10-year period reported about 23.9 cases/year of patients mistakenly ingesting PTP. At our hospital, an average of 5.6 cases were treated annually. When cases not reported in the literature are included, the member may by considerably greater. The reasons for mistaken ingestion include: “took the drug too hastily” “took the drug while talking” and “took the drug mixed with other drug”, suggesting that the patients attention was directed to other factors during the ingestion of the tablets/capsules in many cases.
To prevent the misingestion of PTP, measures are necessary from the drug manufacturer, hospital, and the patient. At Kitasato University East Hospital, an explanatory leaflet for preventing mistaken ingestion of PTP was produced and distributed to patients. After distribution, 75.4% of the patients polled replied that they now realize the danger associated with misingestion and will be more careful from now on. The production and distribution of such explanatory leaflets may by useful for preventing the mistaken ingestion of the PTP by patients.

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As for generic drug, there are acknowleged a few presentation materials of application for production approval to Ministry of Health and Welfare, compared with pioneer drug. In particular, bioequivalence between these products wasn't taken out duty in old application products, and they have been used. Thus, we examined the pharmaceutical equivalence of pioneer and generic drugs (4 products), i. e. timepidium bromide and ketotifen fumarate. Each product conformed to the standard weight deviation, disintegration and quantitative tests according to the Japanese Pharmacopoeia (12 th Ed). However, significant differences were found among the products in the dissolution test for timepidium bromide. The dissolution test is conducted to ensure that the quality of medical supplies meets a fixed standard, and to maintain bioequivalence. Poor results in the dissolution test often result in an attenuation of bioavailability, and may produce differences in absorption compared with other products. Therefore, it is suggested that one product which exhibits a different dissolution profile to other compounds may possess different pharmacokinetics.

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In the present study, we examined the effects of light, temperature and humidity on the residual rate of alfacalcidol in four commercially available preparations of alfacalcidol (Alfarol^® capsules, Alfarol^® powder, Warkmin^® capsules and Onealfa^® tablets). The tests were performed for up to 10 weeks with PTP seals, or without PTP seals. The changes in residual rate of alfacalcidol in Alfarol^® powder packaged with cellophane-laminate paper, and Onealfa^® tablets packaged with cellophane-laminate paper after crushing were also examined.
The residual rate of alfacalcidol decreased in Alfarol^® capsules packaged with PTP seals under fluorescent lighting (1000 lux) and in Alfarol^® powder without an aluminum seal under all conditions. There were no changes in the contents of alfacalcidol in Alfarol^® capsules with PTP seals and Alfarol^® powder packaged by aluminum seal. A slight decrease in the residual rate of alfacalcidol in Warkmin^® capsules was found under fluorescent lighting. The residual rate of alfacalcidol decreased in Onealfa^® tablets under high temperature and/or high humidity. Alfarol^® powder packaged with cellophane-laminate paper and Onealfa^® tablets packaged with cellophane-laminete paper after crushing were found to be unstable, indicating that long-term storage should be avoided when these formulations are prepared.

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Updating drug information was simplified and the issuance period shortened for our hospital formulary developed using a commercially available package-insert drug information database. Recently, Local area network (LAN) system has been improved. So we developed a new World Wide Wed (WWW) edition of the hospital formulary based on the same drug information database so it can be accessed by every client terminal in the university. The drug information database was extracted from a CD-ROM by the syllabary order and the order of the pharmacological category to create index files. The text and index files were converted to Hyper Text Markup Language (HTML) using the text processing software Jgawk. Original drug information created by the hospital pharmacy as DI NEWS, including drug interactions and adverse reactions, were also converted to HTML and linked to the drug in the text.
This formulary was written in HTML, therefore, any kind of client terminal can access this new WWW edition of our hospital formulary on line. Previously, at least 2-3 months were needed to publish a new hospital formulary, however it could be completed within one day by extracting information from a CD-ROM and creating a new edition of the hospital formulary on the WWW server.

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The clinical usefulness of a microparticle enzyme immunoassay (MEIA) method for the determination of dogoxin in serum was investigated. The inter-and intra-assay reproducibilities of this method were 2.4 to 4.9% and 3.8 to 6.2%(C.V.%), respectively.In the determination of serum digoxin levels, MEIA well correlated with fluorescence polarization immunoassay (FPIA) (r=0.942, n=153). Cross reaction by various drugs used concomitantly with digoxin was not detected in the MEIA assay. Moreover, endogenous digoxin-like immunoreactive substance was not detected in serum from newborns (n=24) or patients with renal failure (n=42) who were not taking digoxin.

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A micro method for the determination of pilsicainide hydrochloride, an antiarrhythmic agent, in human serum was developed. In this method, serum containing the drug was extracted with benzene under alkaline conditions and then the extract was analyzed by high-performance liquid chromatography using a 5 mm Shim-pack HRC-CN column (150 mm×4.6 mm I.D.) at 40°C.The mobile phase was 65 mM sodium perchlorate-acetonitrile (85: 15). The flow-rate was kept at 1.2 ml/min and the column effluent was monitored at 200 nm. Lidocaine hydrochloride or disopiramide phosphate was used as an internal standard. The method is accurate and reproducible for routine monitoring of serum pilsicainide hydrochloride.
The serum levels of pilsicainide hydrochloride in 30 patients monitored at 1.2 to 15.5 hrs after the last dose prior to blood sampling varied from 0.18 to 1.52μg/ml. Relatively large interindividual differences were observed in the apparent total body clearances and elimination half-lives estimated using a computer program (PEDA). We recommend that the serum levels of pilsicainide hydrochloride be monitored in patients receiving this drug therapy.

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We have developed a computerized checking system for drug interactions as a subsystem of the dispensing support system linked to the prescription order entry system in Oita Medical University Hospital. Using this system, interactions between two drugs in separate prescriptions can be checked for overlapping administration periods. The outline of the detected interactions can be printed on the prescription. The details (cause, effect, management, reference and so on) of them can be displayed on the computer screen. Two hundred and twenty-nine cases of unfavorable drug interaction have been detected after 3 months of using this system. A revision of the prescription was performed in 20.5% of them, according to the advice from clinical pharmacists.

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Home parenteral nutrition (HPN) improved the quality of life in patients with intestinal failure who had used a long-term total parenteral nutrition. To examine some important factors for a long-term HPN, we analyzed several conditions and quality of life (QOL) for a patient who has received HPNs for more than ten years. In this case, excellent QOL has been maintained for a long period without any undesirable clinical pictures or infections by means of a well-balanced constitutions of lipids and trace elements and good catheter manipulation. These data suggest that HPNs based on the condition of individual patients are the most important factors for long-term HPNs.

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