Recently, it have been reported that many clinical cases have injested insecticides and herbicides either for the purpose of suicide or by mistake, and thet these agricaltural chemicals poison the soil, especially rivers or lakes. Removal of these compounds is thus needed. In this regard, we report herein the application of polyamino acids for the adsorption of these agricultural chemicals by using the quartz-crystal microbalance (QCM) method.
The homopolyamino acids exhigbit a high affinity to malathion. Poly (Leu) adsorbed an equal mass of cyanophos and trifluralin. Accordingly, polyamino acids are expected to be useful as adsorbents for organic phosphorous insecticides and herbicides.

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We studied retrospectively the relationship between the clinical effect of development of side effects and blood cyclosporin (CyA) concentration in patients with psoriasis, based on the blood concentration monitoring data of CyA and the clinical chart. Sixty-five percent of 50 patients received CyA within the range of 3-5 mg/kg/day dose. Although the blood concentration rose as the dose increased, intra-individual variation of the blood concentration of CyA was extremely large. The blood CyA concentration in the patients evaluated as “fully effective” was within the range of 34-297 ng/ml, and that as “insufficiently effective” was 51-375 ng/ml. Based on the evaluation of the individual patients (n=9), the clinical effects were related to the blood CyA concentration in half of the patients. Hypertension (23%) as the side effect appeared with the highest frequency, followed by the reduction of renal function (12%).We found that hypertension developed frequently more over 100 ng/ml and renal function was reduced a more over 180 ng/ml.
In conclusion, It was shown that the blood CyA concentration should be monitored individually, since the optimum concentration for onset of effect was largely different among patients. Furthermore, it was demonstrated that we could advise doctors to ensurer the proper therapy through the blood CyA concentration monitoring in an attempt to avoid the onset of hypertension and renal failure which was dependent on the increasing blood CyA concentration.

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Pharmacokinetic and pharmacodynamic (PK/PD) analyses for a thromboxane synthetase inhibitor, ozagrel, were performed to predict its PK/PD profiles in human. The pharmacodynamics of ozagrel was characterized by serum levels of thromboxane B₂ (TXB₂), a pharmacological marker for thromboxane synthetase inhibition. Based on a quantitative relationship between the plasma ozagrel and serum TXB₂ concentrations after single oral dosage, IC50 and Emax values were estimated to be 11.8 ng/ml and 94%, respectively. The pharmacokinetic parameters of ozagrel were estimated from the plasma ozagrel concentrations after intravenous (iv) bolus, iv infusion, and oral administration at various doses. An integrated, simple PK/PD model was developed to simulate the changes in serum TXB₂ levels after oral administration at various doses, and the obtained simulation curves corresponded well with the observed data. In order to test the predictability of our PK/PD model, the model was then used to predict the changes in serum TXB₂levels after multiple oral administration in human. The predicted curves were in good agreement with the observed date. Thus, the clinical usefulness of the PK/PD modeling was verified for ozagrel.

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The effect of age on pharmacokinetics of MTX after high-dose MTX (HD-MTX) infusions was investigated. Fifty-nine patients (age: 18-83 years) received HD-MTX infusions (dosage: 1.9-3.8g/m³) for 6 hrs. All patients were divided into the following three groups according to their ages: young group (18-29 years), middle-aged group (31-57 years), and elder group (60-83 years). Mean residence time and clearance of MTX obtained by moment analysis showed a significant delay and decrease, respectively, in the elder group among patients, while there was no significance in the steady-state volume of distribution. In addition, a significantly higher concentration and slower elimination during the first 12 hr were observed in the elder group. Significant resultant decrease in renal and hepatic functions were demonstrated on days 2 and 7, respectively, indicating prompt renal damage and delayed hepatic damage in the elder patients.
These results suggest that the pharmacokinetic differences among age groups were evoked by the decreased renal function at the early stage of infusions. Furthermore, drug monitoring in the early stage following the infusion is important for preventing the onset of the severe toxicity common with HD-MTX therapy in the elder patients.

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Bromvalerylurea and coadministered drugs in serum, gastric fluid and urine were measured by HPLC in 10 cases of acute intoxication. In four cases, bromvalerylurea was collected and in six cases, bromvalerylurea and other drugs were collected.
Morover, 5 microgram/ml of bromvalerylurea in serum was suggested to depress the conscious level of patients. Elimination half-lives were 3.6 hr under treatment of forced diuresis. The bromvalerylurea level in the fatal case was 189.4 microgram/ml in serum.

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The effects of gel concentration before drying, thickness of the dried gel sheet and the additives on the water absorption and swelling profile of the dried gel sheet prepared with carrageenan were investigated. The following results were obtained.
The higher gel cocentaration before drying demonstrated the faster water absorption and swelling rate in the carrageenan sheet. The water absorption and swelling rate became 1.3-1.5 times faster with the addition of potassium citrate, sodium citrate and gulcose. However, the thickness of the sheet and the amount of additives scarcely affected the water absorption and swelling profiles.

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The collection of drug information is indispensable for the efficient supply of information, which is the final goal of Drug Information (DI) activities, but the collected information has no significance if it can not be utilized. Therefore, in order to study a time-series survey on how information collected in the DI Room can be utilized and establish a rational information collection and utilization system, we conducted a pilot study on interferon (IFN) preparations, which have been the subject of many questions to the DI Room in recent years.
The study period covered about 16 years from the time when the DI Room was established and collection of information started in 1978 until 1994. The utilization of information was considered to occur when surveys were performed and replies were given to questions on IFN directed to the DI Room during this period. The number of time-series utilizations of collected information and the hit rates, as well as the period from collection until utilization of the information, were calculated.
The study period covered about 16 years from the time when the DI Room was established and collection of information started in 1978 until 1994. The utilization of information was considered to occur when surveys were performed and replies were given to questions on IFN directed to the DI Room during this period. The number of time-series utilizations of collected information and the hit rates, as well as the period from collection until utilization of the information, were calculated.
In the time-series study, differences in the utilization conditions were found depending on the contents of the information. Because new adverse drug reactions suddenly appeared with the increased dose associated with the addition of hepatitis C as an indication of IFN, the number of cases of collection and utilization of information on adverse drug reactions also increased after addition of the indication, and the hit rates for the collected information were quite good. The appearance of new information resulted in a time-series related reduction in the utilization of old information and shortened the time from collection until utilization. Definite information on stability after dissolving of the preparation, the prick test, etc. was utilized no matter what the time of collection.
Because various factors affect the collection and utilization of information, including differences due to the properties of the preparation and the contents of the information, the DI member must bear these factors in mind and endeavor to collect information aimed at the reliable supply of information.

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The guantitative examination of gel formed in the reconstituted solutions from five lyophilized tissue plasminogen activator (t-PA) preparations was performed using a submicron particle analyzer, scanning electron microscopy and size exclusion HPLC. In two preparations containing human serum albumin (HSA), comparatively marked gel formation was observad. These gels were confirmed to be protein-containing products by X-ray emission spectrometry, suggesting that gel formation occurred by denaturation, aggregation and precipitation of t-PA and ingredients, especially HSA. The gel formation was not marked in the preparations to which was added polysorbate 80. Furthermore, the site specific change in the cake structure was observed by scanning electron microscopy, suggesting that gel is formed during the lyophilization process.
In conclusion, the optimal selection of excipient and the lyophilized condition should be desired in pharmaceutical development of the lyophilized t-PA preparation to decrease gel formation.

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The plasma concentrations of carbamazepine (CBZ) and its metabolites, CBZ-10, 11-epoxide (CBZ-E) and 10, 11-dihydro-CBZ-trans-diol (CBZ-T) were measured by HPLC in 81 epileptic patients treated with CBZ alone and with other anticonvulsants, such as phenytoin (PHT), phenobarbital (PB) and sodium valproate (VPA). The following results were obtained. First, the plasma concentration of CBZ decreased, while those of CBZ-E and CBZ-T inversely tended to increase, when it was given together with other anticonvulsants such as PHT and/or PB that induced liver microsomal enzymes. The dose of CBZ in combination therapy with PHT and/or PB was required to be higher than in CBZ monotherapy to maintain the same plasma concentration. Second, when CBZ was given with VPA, the plasma of CBZ-E/CBZ ratio increased, while that of CBZ-T/CBZ-E ratio decreased. This suggests that VPA decreases CBZ-E clearance. Third, this study suggests that the dose of CBZ could be increased to maintain the optimal plasma concentration when it was given with PHT and/or PB. On the other hand, an abnormal elevation of CBZ-E should be noted when CBZ was given with VPA, as there is a possibility that VPA decreases CBZ-E clearance.

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We analysed the adsorption of organic phosphorous insecticides and herbicides by ethylcellulose, acetylcellulose, polysulfone, polystyrene and polyvinylchloride using the quartz-crystal microbalance (QCM). Ethylcellulose had a high affinity for both organic phosphorous insecticides and herbicides. The adsorption capacity of acetylcellulos exhabited a low adsorption except for cyanophos.
Polysulfone and polystyrene featured a high affinity for organic phosphorous insecticides and herbicides which polyvinylchloride had low except for fenitrothion. These results indicate that adsorption of insecticides and herbicide by polymers is affected by the chemical structure of the polymers used.

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An antacid property of Maalox solution and Maalox granule was compared under three different simulation conditions: basal secreting state (0.05N HCl 30ml), high secreting state (0.2N HCl 30ml) and compensative secreting state (0.2N HC1, 10ml add every 10min. to the reacting solution).
Maalox solution exhibited a higher neutralizing point under the high secreting state condition rather than in the basal secreting state condition, and had a higher neutralizing point when the higher concentration of HC1 (0.2N HCl, 10ml) was added in the third condition. Though maalox solution and Maalox granule have the same chemical composition, the two products exhibited a different property on reaction with different concentrations ot HCl.

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In line with development of hospital compounding to one particular orientation in Nagasaki University Hospital, there has been a marked tendency for the decrease in the preparations over all possible orientations compounded beforehand such as ointments or powders. We attempted to evaluate the work involved including the calculation fees for the technica skill needed based on the unit processing of the preparations.
The working tasks that we take preparation for 5 unit processes is 5 points. As a result, we could make a comparative examination of the work required for each preparation on the same scale during the 1990-1994 period. In 1990, the working score for unsterilized preparetions was 34, 742 points and the sterilized preparation score is 46, 744 points.points and the sterilized preparation score is 46, 744 points.
In 1994, the score for unsterilized preparations was 1, 021points whereas that for sterilized preparation grew to 163, 089 points.
At present, the preparations for the condition of a disease are increasing as patient-oriented services. This method of assessment is considered available to reexamine works in the preparation service.

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The relationship between the quantity of antibiotics utilized in classification and the number of cases of methicillin-resistant Staphylococcus aureus (MRSA) in Nagasaki University Hospital was retrospectively investigated during the June 1993 May 1995 period. Notably, the yearly quantity of the third generation cephems gave a good correration for the yearly number of MRSA isolates. In addition, a significant correration was observed for the monthly quantity of the antibiotics which could extend to MRSA using Spearman's rank correlation. The successive terms of the use of monobactums appears to be closely related to an increase in the number of MRSA isolates on statistical consideration. These observations demonstrate the need to limit the furthe rspread of resistance to nosocomial infection.

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