In an attempt to evaluate the reliability of apoenzyme reactivation immunoassay system (ARIS) method, phenobarbital (PB) and phenytoin (PHT) concentrations in patient's serum were measured by ARIS method, and were compared with those obtained by fluorescence polarization immunoassay (FPIA) method and enzyme multiplied immunoassay (EMIT) method.
The within-run precision of ARIS method was 2.56-5.26% as the coefficient of variation (C. V.). The C. V. value of between-run precision was less than 6%. There were significant correlations between the serum concentrations determined by ARIS method and each method (FPIA; EMIT). The interference from hemoglobin, bilirubin, ascorbic acid, flavin adenine dinucleotide (FAD) and cross-reacting substances was also investigated and discussed.
ARIS method was found to be reliable, simple and rapid one. Therefore, ARIS method seemed to be a useful technique for the rapid determination of drug concentration.

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As the therapeutically effective blood level of mexiletine (MX), a recently marketed antiarrhythmic agent, is narrow at 0.5-2.0μg/ ml, the side-effect occurrence rate increases when the blood level of the drug exceeds 2.0μg/ ml. Therefore, close monitoring of the blood level of the drug is required after administration of the drug.
We developed a new method for this measurement using high-performance liquid chromatography (HPLC), which is more convenient than the previous method by gas chromatography. The general procedure is as follows: An internal standard (4-methylmexiletine) is added to the serum sample, followed by the addition of a sodium hydroxide solution, and the whole is mixed well, then injected into an extrelut (manufactured by Merck Co.). The mixture is extracted with diethyl ether, and the extract is evaporated to dryness, and dissolved in an elution solvent, then subjected to the HPLC analysis.
The values obtained by the peak-height method showed a lineality at 0.2-5.0μg/ ml. The recovery rate from the serum, to which MX was added at 2.5μg/ ml, was 80.4-90.0%. Coefficient validity was 3.1%. Good chromatographic data was also obtained in measurement of serum levels in patients administered MX.

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The stabilities and the release of hydrocortisone-17-butyrate (HC-17-B), fluocinonide (FLC), amcinonide (AMC), beclomethasone dipropionate (BCM-DP), triamcinolone acetonide (TCA), betamethasone dipropionate (BM-DP) and betamethasone valerate (BM-V) in admixtures of commercial ointment with boric acid and zinc oxide ointment (BZO) were studied. Determination of several corticosteroids were made by high-performance liquid chromatography.
The stabilities were recorded immediately after admixing and after storage for 2, 4, 8 and 12 weeks at 5°C, 25°C and 40°C. FLC, AMC, BCM-DP and BM-DP were stable in all cases, but after storage for 12 weeks at 40°C, 88.4% of BM-V, 88.6% of TCA and 31.2% of HC-17-B remained in the admixtures. The amounts of all corticosteroids released from commercial ointments admixed with BZO were greater than those from the individual commercial ointments.

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The effect of mixing with other ointment and the ratio of admixture on in vitro release of betamethasone dipropionate (BM-DP) from 4 different model ointment bases were investigated. The bases used included white petrolatum (WP)-purified lanoline bases (I), WP-liquid paraffin bases (II), WP-propylene glycol bases (III) and plastibase (PB) bases (IV). Ointment used for admixture was zinc oxide (10%) ointment (ZO) alone and ointment bases I through IV above. The ratios of admixture were adjusted so that the final concentrations of the mixed ointment were 0, 1/ 4, 2/4 and 3/ 4. The release of BM-DP from the bases was measured by HPLC.
As the amount of BM-DP released fitted Higuchi's equation, the release rate constant (K) was calculated by that equation. Constant K of BM-DP from the model ointments mixed with WP bases (I through III) and PB bases (IV) decreased in proportion to the decrease in BMDP levels, but when the concentration of ZO added was 1/ 4 or 2/ 4, the constant K reached the maximum and gradually decreased thereafter, as it was intended for clinical efficacy.
From the above, it was suggested that this could be a simple but useful method for determination of compatibility and selection of the proper ratios of mixture of corticosteroid ointment with other bases or ointments.

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A method for the determination of serum dimethadione (DMO) was established, using highperformance liquid chromatography, DMO was extracted from human serum with methanol containing α-methyl-α-propylsuccinimide as an internal standard, and chromatographed on a reverse phase column (Shim Pack CLC-ODS) with a mobile phase of acetonitrile/ water (15: 85 v/ v).
This method facilitated DMO determination within 2.4% error over the serum level range from 5 to 300μg/ml, with the limit of detection being 5μEg/ml.

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The effect of various adrenergic agents, adrenaline (Ad), noradrenaline (Nad), phenylephrine (Phe), methoxamine (Methox), isoproterenol (Isop) on ¹⁴C-lidocaine (Lid) absorption, duration of anesthesia, heart rate and ECG were studied in guinea-pigs. The absorption of Lid administered intradermaly at the shaven back was increased with time and its peak was obtained after 70min. Ad (0.1-1.0μg) administered with Lid inhibited about 50-61% of Lid absorption and the duration of Lid-anesthesia was prolonged to 11-56min. Nad, Phe and Methox (moles equivalent to Ad 1.0μg) inhibited 37-45% of the absorption and prolonged the duration of anesthesia for 15-21min. Three-fold dosages of Nad, Phe, Methox however prolonged the duration of anesthesia for about 43-58min. Ad-produced inhibition of Lid-absorption was also observed even at intramuscular administration to the femoral region. The heart rate was increased by Ad 1.0μg at about 50min, but immediately by Isop, together with a slight increase of P-and T-wave, shortening of the P-P interval on ECG. The other compound did not show any effect on the heart rate and ECG.

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The measurement of serum netilmicin (NTL) by substrate labeled fluoroimmunoassay (SLFIA) was evaluated with the purpose to apply to the clinical pharmacokinetic dosing regimen service. Three serum dilution methods including 51-, 16-, and 6-fold dilution factors were used for the measurement based on the method recommended by the manufacture of the assay apparatus and slightly modified by the authors. The maximum within-assay variance (CVw%), between-assay variance (CVb%) and the range of analytical recovery (%) measured by 51-fold dilution method were 4.2%, 11.9% and 102-104%(minimum-maximum values) respectively in NTL concentration ranging from 2 to 10 mcg/ml, but low precision (14.7%), very low reproducibility (30. 2%) and large negative bias (68.5%) were observed in 1 mcg/ml. CVw%, CVb% and the range of recovery (%) by 16-fold dilution method were 6.5%, 12.6% and 104.1-115.6% respectively in NTL concentration ranging from 0.7 to 2mcg/ml, but very low reproducibility (29.3%) was observed in 0.3 mcg/ml. CVw%, CVb% and the range of recovery (%) by 6-fold dilution method were 3.2%, 12.2% and 100.6-119.3% respectively in NTL concentration ranging from 0.3 to 1 mcg/ml. It may be a rational and practical idea with the purpose to apply to NTL dosing regimen that SLFIA-NTL assay of serum NTL concentration should be concomitantly used by 51-fold and 16-fold dilution method. This combination procedure may give accuracy through value and patient pharmacokinetic parameters, therefore, a safe and effective manner of dosing of NTL can be decided.

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For topical application to the treatment of Herpes Zoster, dermatologic cream was prepared from capsule form of rifampicin (Rifadin capsule, 150mg/cap) and external preparation of indometacin (Inteban cream, 10mg/g) by direct kneading. The stabilities of indometacin and rifampicin in the cream were studied at room temperature (24±2°C) on exposure to light, at room temperature under shading and in a cold place (13±2°C) under shading, for 28 days. The amounts of indometacin and rifampicin were determined by high-performance liquid chromatography with UV detecter at 254nm.
The visible change in appearance of the cream and the loss in the amount of indometacin were not observed under these conditions at the end of 28 days of storage. The amount of rifampicin was maintained about 80%of its initial content at room temperature after 28 days. While in a cold place under shading, the amount of rifampicin was maintained more than 90%of its initial content during the period of 28 days. It seems that the cream is a relatively stable and useful hospital preparation for the treatment of Herpes Zoster.

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Extractability from capsule or tablet preparations, and quality test were examined on 5 commercial kalliginogenase products. In extraction from tablet or capsule preparations, we ground them to powder with a small amount of water in a mortar. By this simple method, kalliginogenase could be extracted from each preparation.
The amounts of protein determined by Lowry method were 10 to 100 times more than that of the standard (1μ/ U), but did not correspond to the esteolytic activity measured by BAEE method. Furthermore, one of them was contaminated with trypsin-like protein in the preparation because its esteolytic activity was repressed by a soybean trypsin inhibitor or urinastatin. Therefore, it seems that highly purified kalliginogenase was not used for all commercial products.

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In order to grasp the current status of collecting the articles for literature monitoring of adverse drug reactions (ADR) in DI room and to utilize it as a guide for future activities, we investigated the contents and source of the articles which we ourselves selected, collected and reported in monthly drug information journal of our hospital during the period of 1980-1985. We also analysed the contents and source jounals of the articles describing on ADR which had been collected in our DI room during the past 6 years paying our attention to the drugs most frequently reported in the literatures in 1984, and compared with the results of on-line search using MEDLINE to examine the coverage.
The selecting standard of the articles describing on ADR has been established in our DI room. The articles describing on the terms manifesting ADR symptoms as well as drug name or drug group name in the titles of the articles in particular case reports of ADR are indispensable.
From the analysis of the articles collected according to this selecting standard, it was found that the drug groups most frequently reported in the literatures were 1) central nervous system agents, 2) cardiovascular agents, 3) hormone preparations, 4) antineoplastic agents and 5) antibiotic preparations, and this order showed an almost same tendency through the past 5 years. However, individual drug names most frequently reported in the literatures brought about considerable changes every year. According to the source journals reporting ADR, the four journals, “Lancet”, “Brit. Med. J.”, “J. Am. Med. Assoc.” and “N. Engl. J. Med.” were overwhelming, but Japanese journals reporting ADR were widely distributed without focusing on certain journal.
From the study on the coverage, it was found that the number of articles we collected was apparently less than that of MEDLINE, but we had collected the articles describing on important ADR. This study suggests that the literature monitoring of ADR in DI room will play an important role in early collection and early communication of ADR.

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The qualities of 2 suppositories (A and B) containing 75mg of Ketoprofen on the market were evaluated in the points of weight variation, content uniformity, and release from suppository bases. Release tests were made by the modified method of the rotating basket and the paddle method of J. P. X. In the paddle method, the suppository was put in the cellulose tube (the cellulose tube method) or in the net (the net method). The release fluid was phosphate buffer solution at pH 7.2.
Following results were obtained: 1) The weight variations of both preparations were very small. 2) The content uniformities of both preparations were sufficient. 3) In the rotating basket method, the release of preparation A at 8 hours was about 50%, but that of B was about 20%. 4) In the cellulose tube method, the releases of both preparations at 8 hours were about 40%. 5) In the net method, the release of preparation A at 2 hours was about 100%, that of B at 4 hours was about 75%.

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The clinical utility of fluorescence polarization immunoassay (FPIA) for the determination of serum salicylic acid (SA) concentrations was examined by comparing with high-performance liquid chromatography (HPLC). Results showed that FPIA were considered to be an useful means for the determination of serum SA concentrations in patients received high doses of Aspirin (ASA). It was also found that there was a good correlation between the doses of ASA powder and serum SA concentrations in patients whose blood were taken just before administration (r= 0.85, p<0.01).

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