A simple method was newly designed and compared with a conventional method for the measurement of percutaneous absorption of drugs into human skin from ointments.The ointment was put on the gauze (8×17mm) of a sticky plaster, the rear side of which was covered with a selophan tape, and applied to the human skins.At intervals, the residual drug in the ointment was extracted and measured.The percutaneous absorption of the drug was calculated on the residual drug concentration.The absorption of aspirin from 2% aspirin ointment, which was effective for the cure of postherpetic neuralgia, was investigated by the proposed methods using isopropanol extraction and HPLC determination of the residual aspirin in the ointment.There was no great difference between the absorption of aspirin into the arm and that into the backskin of a normal subject.About 35% of the aspirin was absorbed for 7 hours.A similar absorption pattern was observed in the two patients of postherpetic neuralgia. Thus, the proposed method might be useful for measuring absorption of many other drugs and investigating the effect of bases and accelerators on the absorption into the human skins.

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Dividing property was investigated in scored tablets compressed by direct compression method. For the excipients, lactose (SL), corn starch (CS), synthetic aluminum silicate (SAS), hydroxy propyl starch (HPS), microcrystalline cellulose (MCC) and Perfiller^® were used.Dividing strength of tablet was in the order MCC tablet>Perfiller^® tablet>SAS tablet>SL, HPS and CS tablets.The dividing strength of SL-MCC and SL-Perfiller^® mixture tablets increased with an increase of the mixing rate.But the dividing strength of SL-CS mixture tablet was unchanged.
Weight variation of tablet halves was affected by compaction profiles of excipients alone. MCC, SAS and Perfiller^® showed straight compaction profiles, these tablets had little weight variation of tablet halves.But in the case of SL-CS, SL-MCC and SL-Perfiller^® mixture, no difference of compaction profiles was shown and SL-MCC mixture tablet alone decreased the weight variation of tablet halves of SL tablet. Then a correlation between dividing strength of tablet and weight variation of tablet halves was found in SL-MCC and SL-Perfiller^® mixture tablets.

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Is it possible by computerization of an ambulatory-care pharmacy to decrease outpatient waiting time and to increase the efficiency of the prescription-dispensing process? To improvework flow and reduce outpatient waiting time, we compared the total waiting time of a traditional outpatient pharmacy dispensing system (previous) with that of a computerized dispensing system (current). Various tasks performed in pharmacy are shown Figure 1.Using time recorders, the time taken to perform these tasks was recorded. Three separate weeks, one in July 1989 (previous), one in December 1989 (current) and one in March 1990 (current), were chosen for data collection.
The decrease in waiting time was evaluated comprehensively by determining the average waiting time.the gradient of calculating the arrival time of medicines in pharmacy counter, and minimum and maximum waiting times for every 10 continuous prescriptions (Population. means a group of patients who received their own medicines in pharmacy counter just after lighting of indicator board). In comparison with the traditional system, both the average waiting time and the time to complete the clerical component of the outpatient dispensing process decreased, but maximum waiting time showed no change from the time-distribution curve.Indication of waiting time to each patient should be corrected properly.

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A concentration of digoxin and apparent one of methyldigoxin in serum were measured by using the cloned enzyme donor immunoassay (CEDIA) method and the digoxin-NXT (NXT) method, and compared these new enzyme immunoassay systems with the fluorescence polarization immunoassay (FPIA) method.
There was a significant correlation between FPIA and NXT methods in the serum concentration of digoxin, and a significant correlation between FPIA and CEDIA methods in the serum concentration of digoxin or apparent one of methyldigoxin was also found, respectively.
However, in the serum concentration of digoxin, the mean value of the NXT method was significantly higher than that of the FPIA method.In contrast, the level determined by the CEDIA method was significantly smaller than that by the FPIA method.At the subtherapeutic range measured with the FPIA method (<0.8ng/ml), the value by NXT method shows 1.7-fold higher than that by the CEDIA method.
Cross-reactivities among these three methods were compared by using the serum samples of 15 patients, not administered digitalis.It was found that the determinations of NXT and CEDIA methods were interfered with substances other than digitalis, such as the FPIA method.
These results indicate that the specificity of reaction differs from one another in these three methods.

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We have invented new method to prevent the intra-hospital infections by combination of floor-covering mat and some kinds of disinfectants.
The mat is constituted of the three layers, i.e., a rubber (base), a sponge (middle) and a cotton cloth (surface), as shown in Fig.1.
Bactericidal effects of the mat ( “new mat” ) soaked with disinfectants (chlorhexidine, benzalkonium chloride and alkyl diaminoethyl glycine) were examined, using 51 methicillin resistant Staphylococcus aureus (MRSA) strains isolated from the clinical and environmental origin in Shinshu University Hospital.It was found that the number of the survival bacterial cells on the “new mat” were significantly small during its moisture was kept with disinfectants in comparison with those on the conventional mat.
Removal rate of MRSA on “new mat” was revealed as 60-96%(m.v.76±13.5%) in the investigation by 10 volunteers feet.
These results indicated that the “new mat” was very useful for the protection from the pathogenic organisms.

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A new colorimetric procedure is described for the determination of hydrogen peroxide.This method is based on oxidation reaction between N, N-diethyl-p-phenylenediamine and xanthurenic acid in the presence of peroxidase to form a quinonoid dye.The green chromophore, which is formed in the condition of pH 3.0-4.4, has an absorption peak at 750nm without serum proteins. This system can be utilized for the determination of serum oxalate using oxalate oxidase with the pre-treatment of deproteinization.The determination of serum oxalate can be completed within 15min, and results are linearly related to oxalate concentrations up to 500μM. This procedure is rapid, simple, and precise.

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Enteral hyperalimentation (EH) has been getting popular as one of the ways for hyperalimentation.Administration of EH solution requires a couple of hours (up to about 4 hrs) to be completed.Therefore, drugs in EH solutions must be stable during administration.
Several studies on the stability of drugs in solutions such as physiological saline and 5% glucose for an intravenous infusion have been reported Recent study on photostability of a drug in 5% glucose solution in a ward showed that administration of unstable drug by a continuous infusion resulted in a significant loss of close. Simulation study also showed the influence of unstability of drug on the dose given by a continuous infusion. However, stability of drugs in EH solutions has not been reported yet.In this report, we studied photo-stability of drugs in EH solutions, which is turbid, and assesed the influence of unstability of.drug on the dose given by a continuous infusion.For this study, Clinimeal (CM) and Besvion (BV) were selected as products for EH, and vitamin B₂ and vitamin B₁₂, as photounstable drugs.

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The relation of pediatric doses to body weight and body surface area was examined in patients whose plasma concentrations of phenobarbital, phenytoin, sodium valproate, carbamazepine, and theophylline were monitored.There existed definite correlations between the dose and body weight, or between the dose and body surface area.Among five drugs, the best correlation was obtained in theophylline.Moreover, the dose was correlated better with body surface area than with body weight.
The doses per body weight of phenytoin and theophylline were significantly greater in children with age under 15 years old than in adults over 15 years old, and those of the other drugs also showed a similar tendency.On the other hand, there was no difference in the dose per body surface area between children and adults.The (plasma concentration/dose per body weight) ratios of phenobarbital, phenytoin and theophylline were significantly lower in children than in adults.Consequently, it seems that the doses in patients under therapeutic drug monitoring correlate better with body surface area than with body weight.

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In order to improve the bioavailability of 6-mercaptopurine (6-MP), the elixir and two kinds of suppositories (Witepsol (WH) base and macrogol (MC) base) of 6-MP were prepared and administered to a child with acute lymphoblastic leukemia (ALL) in a balanced crossover design. Plasma levels and the area under the plasm concentration-time curve (AUC) values for 6-MP were determined following the powder, elixir and suppositories administrations of 6-MP. Compared with the AUC value after the powder administration, the relative bioavailabilities (F_ret) for the elixir and suppositories were evaluated, respectively. The concentration of 6-MP in the elixir was prepared to 0.25%.The suppositories of 6-MP were prepared by the fusion method and the content was 20 mg/g/one suppository. The release of 6-MP from the suppositories was examined by the dissolution test in vitro before the clinical study. The release ratio of 6-MP was higher from the MC base suppository than from the WH base suppository. 6-MP was administered orally (50 mg/m²) and rectally (30 mg/m²) to the child with ALL, respectively. The plasma levels of 6-MP were determined by the high-performance liquid chromatography method. The AUC values (ng·hr/ml) from the powder, elixir, WH suppository and MC suppository administrations were 82.3, 204.0, 197.0 and 714.4, respectively.The F_rel for the elixir, WH suppository and MC suppository were 2.48, 3.99 and 14.47, respectively, that was extremely increased by the MC suppository administration.
This finding indicates that the rectal administration by the MC suppository of 6-MP could avoid the first-pass metabolism of this drug, and that this rectal administration of 6-MP will be effective on the treatment of children with ALL, especially for the patients with nausea and/or vomiting.

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By using a hydrophilic vinyl silicone plug, a new method for preparation of hollow type suppository was developed.It has become possible to make a lot of hollow type suppositories at one procedure and to get any volume of cavity by this method.Furthermore any kinds of plastic mold are available to this preparation;its handling is simple;the quality of suppository can be kept constant and this type of suppository is suitable for storage.From the facts mentioned above, this new method is very useful to prepare the hollow type suppository.

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The prescription ordering system has been on-lined to a fully automatic tablet packaging machine in order to transmit the host data for inpatient periodical prescription.In this time, we tried to improve the method of transmitting the host data for prescription and drug files in the data converter, and also tried to change the operating machine for one dose packaging in order to dispense tablets more automatically.
These resulted in the success of the automatic one dose packaging without modifying the host data by hand, even if the amount of drug component or unequal dispensing was inputted to the computer for prescription.Drug files enable to be changed automatically by using the hard disk in case of the partial replacement of tablet cassettes in the fully automatic tablet packaging machine.Moreover, the new operating machine for one dose packaging enables to input the data by hand easier and to record the amount of tablet consumed over all tablets automatically.

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An automated system for printing the drug envelopes has been developed by connecting with the prescription ordering system.The hardware of this system consists of a printer as terminal of the ordering system and a heat-sealing and cutting machine.Informations such as patient's name, directions and dosage, etc.were utilized from the patient database and the ordering database by physician prescribing which were kept in host computer.These data were automatically printed out on the continuous paper, and then the paper was heat-sealed and cut for the drug envelopes.The drug envelopes were produced rapidly and accurately with this system. It was suggested that the developed system was very useful for printing the drug envelopes in hospital pharmacy.

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