The release of indomethacin from 3 kinds of rectal capsules was investigated by 2 different dialysis tubing methods, i.e., stationary method and up-and-down motion method. In the case of stationary method, any release rate of indomethacin from rectal capsules was much slower than that from suppositories, and the amount of the release during 2 hrs was within 8% of the labeled amount. The release of the drug from rectal capsule was not improved by the addition of water into the dialysis tubing, or by sinking deeply the dialysis tubing to spread out the contents in rectal capsule. However, by the up-and-down motion of dialysis tubing using disintegration test apparatus, the release rate was 2-3 times higher than that by the stationary method.The data from this experimental condition was well reproducible. The technique could be applied to test the release of drug from both rectal capsule and suppository.

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A simple, sensitive and specific method of high-performance liquid chromatography (HPLC) was developed for the determination of clonazepam in plasma. Clonazepam in plasma adjusted to the pH range of 8.0-9.0 was extracted with acetone-chloroform mixture (2: 3). The organic layer was evaporated to dryness in vacuo. The residue was dissolved in methanol containing 1-naphthol as internal standard, and a part of the solution was injected into the HPLC system. For the stationary phase, a reversed phase column maintained at 30°C was used. The flow rate of the mobile phase consisted of 0.1 M acetic acid-methanol (65: 35, pH 5.0) was 0.8 ml/min, and the elutes were detected by UV monitoring at 306 nm. In this condition, the peak of clonazepam was excellently separated from that of carbamazepine, and other anticonvulsants which were often administered with clonazepam at the same time did not affect the determination of clonazepam. The calibration curve from peak height ratio was linear and a coefficient of variation was 3.5%(10ng/ml, n=5). The recovery of clonazepam from plasma sample containing 20ng/ml was 99.9±4.6%(mean±S.D., n=5). The limit of detectability for quantitation was 5 ng/ml plasma when 1.0ml of plasma was used.

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Effects of weight variation of powders divided by an automatic packaging machine for dispensing on time-course of simulated blood drug levels were studied. Digoxin and phenytoin (powdered form with excipierits) and sodium valproate (fine granules) as model drugs were packaged by the machine. To simulate weight variation of packaging, normal random deviates were also used.
In case of valproic acid, relatively large variation of the levels to the weight variation was observed, and this phenomenon may be caused by rapid absorption and elimination of drug. However, relatively small variations of that in digoxin and phenytoin were observed, and these phenomena may be caused by slow or saturated elimination of drug. The concept of regression and correlation was applied to the relationship between weight variation and variated blood drug levels as the technique in order to quantify the response. Observed values of the regression and correlation coefficients were 0.08 and 0.18 in phenytoin, 0.15 and 0.56 in digoxin, and 0.52 and 0.88 in valproic acid, respectively. The degrees of effect of weight variation on the variation of blood drug levels resulted from the pharmacokinetic properties of drugs, and the regression and correlation coefficients may be able to use as a decision marker to decide tolerance limits of weight variation of powders in dispensing.

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For the topical application to the treatment of female herpes progenitalis, four different oleaginous ointments containing 3% of vidarabine were prepared with oleaginous bases; plastibase, plastibase with liquid paraffin, plastibase with white petrolatum, and white petrolatum. The amount of vidarabine in each ointment determined by high-performance liquid chromatography with UV detection, was maintained more than 99% of its initial content after 21 days storage at 20°C or 30°C, showing that vidarabine is very stable in each ointment. Consistency of four ointments measured with penetrometer, and spreadability measured with spreadmeter did not change when these ointments were kept at 20°C or 30°C for 21 days.
Among four oleaginous bases, plastibase was the most useful for clinical application, judging from several sensory tests. We also have obtained preliminary results that vidarabine ointment consisting of plastibase was most effective to the treatment of female herpes progenitalis among four ointments that we prepared.

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A method of high-performance liquid chromatography was developed in order to study the pharmacokinetics of cisplatin (CDDP) administration by bronchial artery infusion (BAI). Following ultrafiltration of serum with centrisart I (mol. wt. cut off<10, 000), platinum chelation by N, N-diethyl-dithiocarbamate (DDTC), extraction with chloroform and separation on an octadecylsilane-bonded silica column (TSK gel ODS 120T, 4.6 I.D.×150 mm), the eluted components were detected by UV monitoring at 254 nm. The mobile phase consisted of methanol-chloroform-water (68: 3: 29). Nickel chloride was used as an internal standard.There was a linear relationship between the peak height ratio and the concentration of CDDP in the serum in the range of 0.1 to 10 μg/ml. The detection limit was 0.02 μg/ml (S/N=3) in serum. The overall analytical recovery of CDDP was 78.4-92.2% in the concentration in the range of 0.1 to 10 μg/ml.
Serum concentrations of ultrafiltratable CDDP were determined by following 50 mg/body and 50 mg/m² BAI of CDDP to lung cancer patients, and the effects of the two doses were compared. After BAI, the mean concentration of ultrafiltratable CDDP showed that the drugs behaved according to the rules of the one-compartment open model and the respective halflives were 27.75 min (50 mg/body) and 21.88 min (50 mg/m²), which were significantly different.

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Thiamylal in plasma was measured by using high-performance liquid chromatography (HPLC). Thiamylal was extracted from human plasma with acetonitrile containing phenacetin as an internal standard, and it was chromatographed on a reverse phase column (LiChrosorb RP-18) with a mobile phase of acetonitrile/0.05M NaH₂PO₄ (60: 40). The recovery from plasma lied between 98.8-104.0%.
Plasma thiamylal concentrations of two patients were measured. Thiamylal concentration in plasma was maintained for 8 to 72 hours after administration at the level of 12-17 μg/ml. The elimination rate constant (Ke) was 0.059±0.017 hr^-1 and biological half-life (t¹/₂) was 12.9±3.5hr^-1 (mean±S.D.) in four patients.

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The fluorescence polarization immunoassay (FPIA) method for the determination of serum aprindine (AP) concentrations was evaluated by comparison with HPLC method.The withinrun precision of FPIA method was 4.6-6.8% as the coefficient of variation (C. V.).The C.V. value of between-run precision was 4.1-8.7%.The values of serum AP concentrations determined by FPIA method correlated well with those determined by HPLC method.The correlation coefficient was 0.987.FPIA method, reliable, simple and rapid, seems to be a useful method for routine clinical use.

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Optimization of cream formula containing adriamycin (ADR) and medroxyprogesterone acetate was investigated.In preliminary experiments, rape seed oil, peanut oil, liquid paraffin, castor oil, sesame oil and hydroxypropylcellulose-H were tested as a base of cream.Rape seed oil was chosen as oil phase of cream because of its spreadability, strength of cream, and suitable particle size of oil in cream.
In order to find the best formula of cream, ten model formulas were prepared according to composite experimental design.Spreadability, strength and stability of cream and ADR stability were measured as characteristics of cream.These characteristics were predicted from a second order polynomial regression equation.The predicted values of characteristics were agreed well with experimental data.The results suggest the usefulness of this method for a quantitative optimization of cream formula.

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Package insert is used primarily as a source of information for drug action, indication, dosage, formulation, adverse reaction and interaction.Therefore, the package insert is frequently revised to offer the most recent information.Questionnaires on the revision of package inserts were sent to 105 manufacturers of 1638 drugs used in our hospital.Frofn.January 1985 to June 1986, 1180 package inserts (72%) had been revised once or more.The most frequently revised information was “precautions for use” .In drug information center of our hospital pharmacy, only 284 of the revised 1514 package inserts (19%) were obtained in this period.The time required to obtain the revised package inserts was relatively long, 3.8 months on the average.Subsequently, a computer-assisted system for maintaining package inserts was developed and implemented from September 1986.In the twelve-months from April 1987 after the implementation of the new system, the acquisition rate of the revised package inserts was enhanced by 69%.The average time required to obtain the revised package inserts was 3.0 months.This system seems to be effective in fulfillment of drug information service by the revised package inserts.

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Concentrations of sodium (Na) and potassium (K), and osmolality (OSM) of 6 human serum albumin (HSA) injections obtained from each pharmaceutical manufacturer were determined. The concentrations of Na and K were determined by atomic absorption spectrometry, and OSM was analyzed with freezing point method.The reproducibilities of Na, K and OSM determinations were about 2, 4 and 2%, respectively.
The determined data were compared with each value informed from 6 manufacturers.In Na concentrations of all HSA injections, there were no significant differences between the data and indicated ones on the packages (p<0.01).However, coefficient of variation (CV) value of 3 lots in one product was 13%.The concentrations of K determined in 4 products were different from those informed from each manufacturer;furthermore the CV values of 5 products were more than 19%.The CV values of OSM of 4 products were less than 5%, but those of 2 products were 13 and 16%, respectively.The ratios of OSM of 2 HSA injections to normal saline were less than indicated values on each package inserts.

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Powders and granules consisted of 20% aminophylline were prepared to improve physical properties of aminophylline powder.Two percent of sodium carboxymethyl cellulose (CMCNa), 5% of polyvinylpyrrolidone K-90 (PVP) and 5% of starch paste were used as binders to make granules of 20% aminophylline.Distribution of particle size of all six different aminophylline granules conformed to standards prescribed in Japanese Pharmacopoeia (JP).Values of angle of repose and grouping rate of granules of 20% aminophylline were lower than those of aminophylline powders, indicating that flowabilities of granules were higher than those of powders.
The powders and the granules did not change in appearance for 30 days under severe condition (at 30°C, relative humidity of 92%).Content of aminophylline in each preparation was measured by absorption spectrophotmetry at 273nm.Among several preparations we tested, both aminophylline powders and granules with D-mannitol as a diluent were most stable for 30 days under severe condition.Disintegration time of the granules was within 10 minutes in water at 37°C.Dissolution test of the granules by paddle method showed a rapid release of aminophylline into water, indicating that bioavailability of the granules may be similar to that of aminophylline powders.From the results of this study, it is expected that 20% aminophylline granule with D-mannitol as a diluent is useful as a hospital preparation.

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A questionnaire was used to ascertain the awareness of pharmacy students (below: p.students) about the practices and business in their field at hospitals.The subjects of this survey were 513 p.students who had participated in practical training at the Pharmacy Department of Kitasato University Hospital during the last 5 years.
1.Most of the students participated in practical training at hospital pharmacies were hoping to become hospital pharmacists, and their experience through the practical training was a basis for their choice of occupation.2.Their comprehensions of pharmacist and job content at hospital pharmacies were low. 3.Through their experience at hospital pharmacies, most students realized the heavy responsibility of pharmacists and the necessity of applied pharmaceutical knowledge. 4.It is necessary to add practical training at hospital to the curriculam at pharmacy school for students hoping to work at hospital pharmacies.5.Cooperation of the specialists in this field is expected to reduce the heavy duty of the pharmacists at the hospital.

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Ethanolamine oleate injection containing 30% iopamiron 300 (30% IP 300-E0) has been previously prepared for endoscopic sclerotherapy of esophageal varices on X-ray TV monitor. However, the ability of fluoroscopic visualization of this sclerosing agent was slightly insufficient in clinical use.We prepared ethanolamine oleate injection containing 30% iopamiron 370 (30% IP 370-E0), and measured the physical characteristics such as viscosity and osmotic pressure of this agent.The ability of visualization was observed in patients with esophageal varix by X-ray.
The viscosity, which was inversely related to the injectability into varices, of 30% IP 370-E0 was relatively low and its osmotic nressure was almost the same as that of normal saline.30% IP 370-E0 was easily injected into varices.Better fluoroscopic visualization was obtained by intravariceal injection with 30% IP 370-E0 than with 30% IP 300-E0.These results suggest that 30% 1P370-E0 is more useful agent for endoscopic sclerotherapy of esophageal varices.

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