The bactericidal effects of commonly used disinfectants against clinically isolated bacteria were examined by the applied method of phenol coefficient measurement. The bacteria examined were 4 species of the clinically isolated strain, E. coli, P. aeruginosa, K. Pneumoniae and S. aureus, which were known to be the main bacteria causing the opportunistic infection. The bacterial broth was put into various concentrations of 9 different disinfectants, and each was inoculated into a fresh medium after 0.5, 2, 5, 15 and 30 minutes. This experiment revealed that there were many ineffective cases in the generally used concentrations.
We also did a questionnaire survey regarding the preparation and usage of disinfectants. The result showed that in many cases the preparation of disinfectant was made by eye measure, which might cause inaccurate concentrations. Therefore, we hospital pharmacists should be more concerned with hospital disinfection.

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Theophylline concentration of plasma from asthmatic patients was determined by newly developed substrate-labeled fluorescent immunoassay with monoclonal antibody (MC-SLFIA method). The results were compared with those obtained by high-performance liquid chromatography (HPLC) and substrate-labeled fluorescent immunoassay with rabbit antiserum (RA-SLFIA method).The coefficient of variation of 10 replicate analysis by MC-SLFIA method using theophylline spiked samples (5μg/ml land 15μg/ml) was less than 5%. There was a good correlation of both determinations between MC-SLFIA method and HPLC (n=73, r=0.994, p<0.001). Cross reactivity of MC-SLFIA method was studied using 9 different theophylline analogous compounds and estimated to increase the measured theophylline concentration by 20% when added to normal human plasma containing 15μg/ml of the drug. The cross reactivity was relatively small such as 200μg/ml for caffeine and 1, 3-dimethyluric acid. These findings show that MC-SLFIA method is a good method for clinical theophylline level monitoring with low cross reactivity, especially to some theophylline metabolites.

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The TDX^R system based upon fluorescence polarization immunoassay was used for therapeutic drug monitoring of methotrexate in serum. This system was evaluated for utility as well as precision and a test-dose method for individual dosage regimen adjustments in high-dose methotrexate therapy.
A comparison of the TDX system to enzyme immunoassay (EMIT^R sytem), which has been used for methotrexate assay, was made on 93 specimens; as a result, excellent correlation, r=0.998. The day-to-day precision was established by 8 replicated analyses during 2 weeks, where coefficient of variation was 0.72 to 2.56% of the within-day precision, CVs was 0.61 to 2.69%.
A study was made to determine if test-dose bolus injection could be used to predict infusion plateau methotrexate concentration. Small nontoxic dose of methotrexate (50mg/ m²) was given to patients who were followed for 24 hr. and the pharmacokinetic data were used to dose modification of high-dose methotrexate infusion.
We used 2 methods of assuming linear kinetics, the pharmacokinetic parameter and total body methotrexate clearance derived from the test-dose data, which can be used to predict infusion plateau methotrexate concentration. We have good prediction from pharmacokinetic parameter of 2 compartment models. It is concluded that test-dose method can be a useful guide to allow appropriate dose modification of high-dose methotrexate therapy.

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The antibacterial activity of antibiotics and the stability of vitamins in 8 transfusions mixed with antibiotics and multi-vitamin infusion (M. V. I.) were investigated and the following results were obtained. No change in appearance was observed 24 hr after the combination of antibiotics and M. V. I. pH was changed only when antibiotics and M. V. I. were mixed in 5 % Klinit. When mitomycin C was mixed in EL #3, Paremental A, Paremental B, Hicaliq #1 or Hicaliq #2, the lowering of antibacterial activity of mitomycin C was observed regardless of the presence of M. V. I. Vitamin A in Moriamin SN or Hicaliq #1 was decomposed by light. Vitamin B1 was decomposed with amino acid products such as Proteamin 12X and Moriamin SN, but this decomposition was decreased in the presence of rolitetracycline. Vitamin B₂ and Vitamin C were stable in the presence of transfusions and antibiotics.

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Four kinds of fat emulsions for intravenous injection in the market were preserved under the following three conditions: at 7°, 20° and 30°C in light-resistant containers. Under these conditions the time-course changes in a particle shape, pH, peroxide and free fatty acid were studied for 6 months. No time-course changes in the particle shape were observed in all of 4 products at the 3 different temperatures while pH value was decreased slightly with time at 30°C. No significant difference was observed in peroxide at any of the temperatures, but free fatty acid concentration was apparently increased at 30°C. From these results, it seems that fat emulsions for intravenous injection is recommended to be kept in a cold place.

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Following the previous study, the prediction method of incompatibility in the case of 2 kinds of injection in a single infusion was investigated by estimating the pH of the admixture solution. Data of the previous paper, such as pH characteristic curves (pH titration curves), positive or negative equivalent values (strength of acidity or alkalinity) and values of incompatible pH were also used in the present study.
The pH of the admixture was determined on the pH characteristic curve of the injection having the most dominant buffer action, by plotting the sum of equivalent values for the other 2 preparations. The change in appearance of 2 injections in a single infusion was predicted by comparing the estimated pH of the admixture with the incompatible pH for each of injections.
From the above results, it was confirmed that the inocmpatibility for the admixture of 3 preparations could also be predicted by using pH characteristic curves, equivalent values and values of incompatible pH for each injection.

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In our previous report(lst Report), study was made on the stability of an injectable solution (EOMA) to be used in injection sclerotherapy (endoscopic embolization) for esophageal varix, which was prepared by mixing Ethanolamine Oleate Injection (EO) with a contrast medium, meglumine amidotrizoate injection.
In the present study (2nd Report), another injectable solution (EOI) was prepared by mixing EO with non-ionic iopamidol injecion. With sterilized and unsterilized samples of EOI, observation was made on time-course changes in appearance, pH and the volume of each component for 8 weeks. Also, mucosity and osmotic pressure of EOI, EO and EOMA were measured.
Except for slight development of a brown color in sterilized samples of EOI, no major change was observed in each test item during the 8-week storage in a dark and cold place. The results suggest that EOI is stable for at least 8 weeks in a dark, cold place. As the mucosity of EOI is lower than that of EOMA, EOI has great advantages in the filtration operation in manufacturing process of injections or in injection into affected parts.

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Many benzodiazepines have valuable anticonvulsant properties. The regular monitoring of plasma concentration of benzodiazepine derivatives during treatment with the drug appears not only useful but necessary, because of the narrow therapeutic iange and risk of increased occurrence of seizure in cases of overdosage.
We studied a high-performance liquid chromatographic method for the simultaneous quantification of 3 benzodiazepine derivatives in plasma. After a single extraction of the drugs from alkaline plasma, nitrazepam, clonazepam and diazepam can be resolved and quantified by using an ODS reversed phase column with 2 volumes of acetnitrile and 5 volumes of 1% triethylamine-phosphoric acid solution (pH 3.0) as mobile phase. By adding triethylamine to mobile phase, retention time can be shortened for diazepam and the other benzodiazepines can also be separated completely. The eluted drugs were detected by their absorption at 254 nm. With this method, it is possible to quantify as little as 6 ng/ml foe nitrazepam and clonazepam, 18ng/ml for diazepam with 1ml plasma samples. Complete chromatographic resolution of the benzodiazepines resulted, permitting quantification of all being done within 30 min. The standard curves showed good linearity with ranges 6 to 400ng/ml for nitrazepam and clonazepam, and 18 to 1000 ng/ml for diazepam.
The day-to-day precision, established by 10 replicate analyses, yielded CVs of 4.5 to 5.0%. Analytical recovery of each drugs added toplasma was complete (95 to 99%). The most common antiepileptics and plasma components did not intefere with the analysis.

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The quality of commercial furosemide sustained-release preparation was evaluated by 3 tests, dissolution, weight variation and content uniformity.
The dissolution test was made with the USP dissolution tester in pH shift test solution with 0.25% Tween 80 added in consideration of acidity in the gastrointestinal tract, and in the 2nd fluid (pH 6.8) in JP X disintegration test. The weight variation test was made according to the method prescribed in JP X In the content uniformity test furosemide was dissolved in 0.1 N-NaOH solution. The following results were obtained. 1) 100% dissolution time was about 5 hours for both test solutions. 2) The weight variation was very small. 3) The mean content was about 98%.

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Primidone (PRM) concentrations in patients' serum as well as in spiked serum samples determined by the methods of high-performance liquid chromatography (HPLC), homogeneous enzyme immunoassay (EMIT) and fluorescence polarization immunoassay (FPIA) were compared in order to examine the reliability of the manual and semiautomatic (SLFIA) method using AMES TDA antiepileptic drug kit. Results showed that both of the SLFIA techniques are useful means for the determination of blood concentrations of PRM in epileptic patients to satisfy the clinical requirements.

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Digoxin is one of the most important drugs in clinical therapeutics. Due to narrow therapeutic range, fine dose adjustment is indispensable, especially in pediatric patients, in the aged and in patients with renal failure. In order to dispense the dose more precisely and easily, 0.01% digoxin powder (0.01% powder) was prepared and the pharmaceutical property was examined. The 0.01% digoxin powder was prepared by diluting the commercial 0.1 % digoxin powder preparation with fine lactose. The bioavailability of 0.01% powder was obtained by comparing area under the curve (AUC) after oral administration of the 0.01% powder 5.0g (as digoxin 0.5mg) with AUC after intravenous administration in 4 healthy normal volunteers.
Our data showed the good content uniformity and rapid solubility (91.3% at 60 minutes) of 0.01% powder. The mean peak plasma concentration was 3.19 ng/ml at 41.3 minutes after oral administration. The bioavailability obtained from AUC time 0 through 8 hours and time 0 through 24 hours was 55.3% and 65.1%, respectively. The mean steady state plasma concentration after oral administration of 0.25 mg/day for 10 days did not show any significant difference between the 0.01% powder and a commercially available tablet.
We conclude the 0.01% powder is a safe and effective alternative of current preparations.

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5% Fructose solution in a pot, given orally to neonates, was found to be contaminated with Acinetobacter calcoaceticus. This contamination was due to continuous use of the pot without disinfection. The following facts were noted:(1) The contamination level of 5 % fructose solution always reached to the order as high as 10⁴ colony forming units/ml immediately before 24-hourly replacement;(2) 10% Fructose solution for injection and distilled hot water for preparation of 5 % Fructose solution were not contaminated;(3) 5 %-Fructose solution supported the growth of the bacilli; that fact was confirmed by challenging test.
It was suggested that the bacilli present in residue of 5 % fructose solution in the empty pot should have multiplied in the freshly refilled solution.

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