The fluorescence polarization immunoassay (FPIA) for measuring serum digoxin levels provides many advantages such as reagent stability and shorter analysis time when compared with other methods. However, the method gives lower digoxin value. This discrepancy may be due to the difference of protein concentration between the digoxin calibrator and patient's serum. We have studied the effect of protein concentration on digoxin level in assaying specimen by the FPIA. It was found that as protein concentration is reduced, digoxin level is increased. The measured digoxin level was particularly higher in solutions when protein concentration was below 5g/dl.
The interference caused by the presence of protein in the dogixin measurement was suppressed by diluting sample with normal saline. The dilution rate was determined in the effort for minimizing the protein concentration difference between the digoxin calibrator and patient's serum. Serum samples of 80 patients were examined for digoxin level by the conventional method and the dilution method of FPIA, as well as by EIA and RIA. The digoxin levels measured by the FPIA dilution method were 20.1% higher on average than those by the FPIA conventional method. Results of the FPIA dilution method correlated well with those of EIA and RIA.
Thus patient's serum with a normal protein range always showed low digoxin levels in the measurement by the FPIA conventional method. We conclude that the FPIA solution method gives relatively accurate results.

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Weight variation test, disintegration test, and dissolution test were made as quality tests for 6 different preparations of griseofulvin. In the dissolution test, water/ethanol (1: 2, v/v) mixture and double-layer solution of water/n-octanol (1:1), water/benzene (1: 1) or water/ethyl acetate (1: 1) were used as dissolution mediums. The absorption of griseofulvin was studied by measuring the blood concentration in rabbits.
The dissolution rates and the parameters of the blood levels were different among the preparations. However, the correlation was observed between the. results of the dissolution test using the water/n-octanol solution as dissolution medium and the AUC-time curve calculated from the blood concentration in rabbits.

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A new reagent kit for serum primidone (PMD) assay by laser immunochemical system (i-PiT) was developed. This kit is different from the former kits in that it uses a drug-linked latex, which reacts with antibody to bring about agglutination and, according to the manual, blank test is unnecessary in the process of assay. First, we confirmed the ground for the omission of blank test in some experiments, and then studied the precision, accuracy and other features of i-PiT method using the reagent kit for serum PMD assay.
The precision of i-PiT method without blank test applied to three-PMD-level specimens of patients, expressed as coefficient of variation, was not less than 8.0% of within-day and not more than 6.0% of between-run. Mean recovery of PMD was 101.2%. Moreover, to study the accuracy, PMD concentration in the sera of 20 patients was determined by i-PiT and EMIT methods. The correlation coefficient and the regression line were 0.978 and y= 0.983x+ 0.181 (y: i-PiT, x: EMIT), respectively.
In consideration of the omission of blank test, precision and accuracy, the new reagent kit for serum PMD assay of i-PiT method is considered to be one of the useful reagent kits for determination of serum drug concentration in hospital laboratories.

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Determination of lower level of serum phenytoin (PHT) was made by homogeneous enzyme immunoassay (Emit) in the following methods:(A) Wide range calibration method, (B) Extrapolated calibration method, and (C) Mixed sample method. In the method A and B, calibration curves of serum PHT levels were generated using a nonlinear least-squares regression program (EMITFIT) with a microcomputer. It was concluded that method A was most reliable of the three. In method A, the PHT recoveries in spiked serum samples in the concentrations of 0.25, 0.5, 1.0 μg/ml were 104.6, 102.6, 100.1%, and coefficients of variation were 11.4, 6.8, 2.3%, respectively.

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Quality tests were made on a Chinese medicine preparation “Unseiin” extract containing 8 crude drugs. The principal components were separated and determined by high performance liquid chromatography, gas chromatography and thin-layer chromatography-densitometry system. Composition of 6 commercial prescription products was as follows (in mg/g): ligustilide 0.01-1.30, paeoniflorin 0.10-4.63, berberine 1.25-4.35, palmatine 0.41-2.65, coptisine 0.36-2.29, woogonin 2.30-5.16, geniposide 1.53-6.12. The content variations among the products of manufacturer A in 4 different lots were comparatively small.
The stability of the extracts on storage was examined in use of several pakaging materials in hospital pharmacy. The extracts are highly hygroscopic, and a special attention should be paid to packaging materials, storage conditions and other factors.

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Permeability of artificial membranes to tegaful in suppositories was investigated by using the dissolution apparatus in the paddle method of JP X, Sartorius absorption simulator and a suppository release apparatus. Pemeability was evaluated on the basis of the release of tegaful from suppositories through cellophane and lipid membranes. Five products (A-1, A-2, B-1, B-2 and C) of tegaful suppositories from 3 manufacturers were used.
The release of tegaful from product A-2 and B-2 in the method using the dissolution apparatus and the suppository release apparatus was significantly more rapid than that from the remaining products. The release of tegaful from product B-2 with Sartorium absorption simulator was also significantly more rapid than that from product A-1 and C. The similar results were obtained in 3 methods. Therefore, this study suggests that the dissolution apparatus in the paddle method of JP X be applicable for evaluation of the release of tegaful from suppositories.

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A high performance liquid chromatography (HPLC) was used for the determination of urinary pipemidic acid (PPA). PPA was chromatographed as ion pairs with ethanesulphonic acid by use of Finepack SIL C₁₈-10 reverse phase column. The amount of PPA was determined by the peak height ratio. The coefficients of variation at within-run were 1.77%(50 μg/ml) and 2.83%(1200 μg/ml), and at between-run were 8.77%(50 μg/ml) and 3.34%(1200 μg/ml).
The urinary levels of PPA after oral administration of 500 mg to healthy male subjects were measured and pharmacokinetics of PPA were studied. The mean elimination rate constant (ke) was 0.27±0. 02 h^-1, biological half-life (t_1/2) was 2.6±0.16 h, and the maximal time of the elimination rate (T_max) was 2.5±1 h. It was confirmed that the urinary levels of PPA determined by this method agree well with those by bioassay.

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Pharmaceutical properties of 6 commercial products of 0.02% fluorometholone ophthalmic suspension were studied. The following results were obtained:
1) All the products had similar pH values and osmotic pressures within the appropriate range, except one product which showed very high viscosity. 2) Foam might have been generated by shaking in dropped eye lotions. 3) The products in small particle sizes seemed to show a good suspension. 4) Four products were redispersed by not more than 5 shakings, while the remaining products required about 10 to 30 shakings.
Redispersion of all the products was affected by temperature and standing time. Large visible particles were observed occasionally in 4 products when allowed to stand at 60°.

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Comparative tests were made of 6 commercial products of 0.02% fluorometholone ophthalmic suspension in terms of the quantity, content, distribution of particle size, etc. by HPLC method. The results were as follows:
1) Some products showed smaller contents than the labelled amounts, although all samples had little deviation of content and quantity. 2) In all samples, the particles smaller than 32μm composed more than 90% of total. But in some products, a few particles larger than 32μm, produced by aggregation, were observed. 3) The number of shakings required for complete dispersion was larger than that given on observation.

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Stability of nifedipine preparations was studied using samples of 5 brands. The samples were kept in 2 different conditions: one group exposed direct to the sunlight and the other under fluorescent light in or out of a blister pack. Changes in appearance, weight and content were examined of the samples kept under the direct sunlight for 3 months and those kept under the fluorescent light for 6 months. GLC, as well as TLC, methods were used for the analysis of nifedipine.
Among the samples taken out of a blister pack and exposed to the direct sunlight, those in lightproof red capsules were stable with little loss in content. No changes were observed in the samples kept in a blister pack under the fluorescent light. However, in some of the sampies out of a blister pack under the fluorescent light, oozing out of nifedipine on the surface of capsules and a considerable content loss were observed as compared with the samples out of a blister pack under the direct sunlight. These results suggest that loss in nifedipine content in soft capsules be not only due to the influence of light.

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Therapeutic drug monitoring (TDM) has been widely practiced in the clinical field. TDM requires the concentration of a drug in a steady state. In order to obtain reliable results of TDM, patients should take medicine according to physician's direction. We have studied the factors which have effect on patient's compliance by interviewing 640 patients. As a result, the average ratio of patient's compliance was about 40%. From this study 3 factors which increase patient's compliance and 4 factors which have little effect have been selected, as follows:
A) Factors which increse patient's compliance: 1) Patient's recognition of the importance of medication. 2) Patient's refraining from discretion in taking. medicine. 3) Keeping exactly the frequency of daily medication.
B) Factors which have little effect: 1) Frequency of daily medication. 2) Period of medication. 3) Kind of medicine. 4) Concern about the adverse effect of medicine.
In addition, the ratio of patient's compliance varied with the kind of disease. For example, the ratio was high among tuberculous patients and low among hypertensive patients.

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Patients' compliance is indispensable for a successful. drug therapy. In this study, we made inquiries about the present condition of patients' compliance and liking for drugs and dosage forms. Questionnaires were sent to 624 outpatients at 9 hospitals in 4 regions, Hokkaido, Iwate, Hiroshima and Fukuoka.
59.1% of the patients took drugs in accordance with physicians' instructions. Easiness of drug taking by dosage form decreased in the order as follows: tablets>capsules>syrups>powders, indicating that tablets are the most desirable and powders the most undesirable. Easiness of swallowing proved to be an important factor in easiness of taking. As for tablets, patients had preference for small-sized, white or light colored tablets. Ordinary round tablets were preferred to peculiarly shaped ones. As for frequency of taking, many outpatients favored fewer times.

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