The effect of psychotropics on the transport of lithium across the erythrocyte membrane was investigated in vitro. The erythrocytes collected from healthy volunteers were incubated in an isotonic-buffered medium containing lithium and psychotropic drug, and the lithium concentration in erythrocytes was measured. Chlorpromazine and levomepromazine significantly elevated the erythrocyte lithium concentration; however, haloperidol, sulpiride and diazepam caused no change of the lithium concentration in the erythrocytes. On the other hand, among the tricyclic antidepressants structurally similar to phenothiazine, clomipramine significantly elevated the concentration of erythrocyte lithium, while imipramine and amitriptyline had no change. Despite that clomipramine, imipramine and amitriptyline have the similarity of chemical struture, the effect of these drugs on the erythrocyte membrane transport of lithium varied. The present results showed that the effect of tricyclic agents on uptake of lithium across the erythrocyte membrane seemed to be related with the presence of a side chain.

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Heterogeneous enzyme immunoassay kit “MARKIT” (Dainippon Pharmaceutical Co., Ltd.) for the determination of carbamazepine (CBZ) and valproic acid (VPA) in the blood of patients with epilepsy was evaluated.
The plasma CBZ and VPA levels measured by the MARKIT method and gas liquid chromatographymethod (GLC) were correlated wel; the correlation coefficients of the MARKIT method were 0.95 for CBZ (n=30) and 0.98 for VPA (n=30) and coefficients of variation intra-and inter-assays for 3 levels of CBZ or VPA were less than 10%. Calibration of plasma CBZ or VPA levels by using programmed micro-computer was more rapid and accurate than that by the manual method, where individual variation for generation of a standard curve was omitted. Relationship between plasma CBZ or VPA levels and daily dosage of VPA or CBZ was unpredictable due to individual difference amoung patients and, therefore, therapeutic monitoring of these drugs was necessary.

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Optimal digoxin therapy has been facilitated by the development of an enzyme immunoassay (EIA) kit for digoxin by monitoring its blood concentrations. Clinically, there were some cases responsive to digoxin at the serum level of 0.3 ng/ml or less. However, at present, no EIA kit can determine such concentrations accurately and precisely. Thus, we conducted astudy on the determination of the lower levels of digoxin by a modified MARKIT method (one of the competitive binding EIA) by using a dilution method of antibody. The results showed that the modified MARKIT method can be clinically used for an accurate and precise (CV 10%) determination of the serum digoxin levels of 0.1 to 2.0ng/ml.

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Pharmacists make much efforts to prevent dispensing errors, but actually they cannot avoid such errors. In order to prevent dispensing errors in supply powder preparations to shelf bottle as well as in dispensing and inspection of divided powders, a computerized inspection system was developed. This system is in the marking system with use of barcode in which the drug tariff code established by the Ministry of Health and Welfare is adopted.
Features of the computerized inspection system of dispensing of powder are as follows: 1.It becomes possible to supply powder preparations to shelf bottle exactly. 2. Powder dispensing can be made perfectly by confirming compounding information (maximal dose, permissive weighing error, incompatibility, etc.) in data base, listening to voice recorder for identification of drug name, and keeping record of weighing powder on digital scale and real drug name by barcode. 3. Dispensing error is removed by utilizing console CRT or hard copy of checking prescriptions.

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Because of dependence upon human senses, conventional inspection of dispensing is not successful to find errors, especially in dispensing powder. Some studies to compare conventional inspection with computerized one, whose specification was described in the first paper, found the latter more effective in prevention of dispensing errors exactly.
The result is as follows. In conventional inspection, it was difficult to check dispensing error since supplying powder preparations to the shelf bottles is made uniformly, and some of dispensing errors are sometimes passed over, which contains failure to select the shelf bottle, to weigh the powder and to check the maximal dose and incompatibility.
This comparison showed many advantages of computerized inspection system. Using a computer made it possible to supply the powder preparations precisely. By utilizing console CRT or hard copy checking prescription, it was possible to prevent various dispensing errors. These data suggest that application of computerized inspection system makes it possible to dispense the powder more precisely than conventional way.

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This report presents the results of case study through questionnaires regarding drug information (DI) service of hospital pharmacy. Questionnaires were sent to 192, 90 and 61 doctors of different hospitals, A, B and C. The following is the study results:
1. Doctors of hospital A who expected DI service to provide more detailed DI than package insert exceeded the number of doctors of hospital B. DI service of both hospitals could satisfy the needs of doctors in most cases, but one of the problems revealed was that doctors were sometimes not able to obtain information that satisfies them. Doctors pointed out that information supplied by hospital pharmacy was no better than information given in package insert. 2. The rate of doctors who had not inquired on the ground of the lack of DI in hospital pharmacy was higher in hospital B than in hospital A. 3. The reasons why the doctors take advantage of DI service of hospital pharmacy as pointed out by doctors of hospital A were varied, including “convenience, ” “readiness, ” “detailed information” and “objectiveness.” Reasons given by doctors of hospital B rather concentrated on certain points, eg, “readiness.” 4. Doctors of hospital C received information both on revision of inserted drug description and on “adverse reaction to drugs” more frequently than doctors of hospital A and B.

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The assay of free form of valproic acid (VPA) in serum was made on 71 serum specimens of epileptic patients. For the isolation of free VPA, ultrafiltration using micropartition system MPS-1 (Amicon Corp.) was applied and it was confirmed that this system was good in utility. For the lower levels of VPA as in ultrafiltrates, a modified single dilution technique was developed in EMIT assay instead of the standard double dilution procedure. The results were compared with those determined by the gas-liquid chromatography. Results determined by the above two methods were correlated well (r=0.982) and the regression line was y=1.023x-0.143. Ultrafiltration using MPS-1 is very simple and practical, because it requires small amount of serum sample. In 20 serum specimens from patients treated with VPA alone, the mean percentage of free VPA was 12.5±3.9%. The percentage of free VPA and total VPA levels showed a positive correlation (r=0.808).

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The stability of sodium latamoxef (Shiomarin; LMOX) in aqueous solution, a newly developed oxacephem antibiotic for injection, was tested at 5°, room temperature (20±5°), and 37°. Decomposition products were studied with thin-layer chromatography, bioautography and spectrophotometry. Furthermore, the residual potency was determined by a microbiological assay (cylinder-plate method). The results were as follows:
1) LMOX (1g (potenty)/10ml) aqueous solution showed changes in color, without any variation in pH after 7 days. Its residual potency after 7 days was 95.1%. The residual potencies after 24 hours were 99.0% at 5° with increased color intensity, 96.5% at 20° and 82.6% at 37°. 2) Aqueous solution of LMOX showed no color change at pH 3.60, but developed a light brown color at pH 8.00 and a light blue color at pH 10.00. No decrease in potency was observed after 24 hours at pH 3.60-10.10 at 5° or pH 3.60-9.00 at 20° and after 6 hours at pH 3.60-10.00 at 37°.

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In order to examine changes in sodium latamoxef (6059-S; LMOX) due to compounding, it was mixed in solution with each of 26 different commercial replacement fluids and 70 different injections. In addition, changes in the mixed injections containing replacement fluids actually used in wards were examined for stability. Decomposition products were investigated by thin-layer chromatography and bioautography, and the residual potency was determined by the microbiological assay (cylinder-plate method).
Aqueous solutions of LMOX were stable in the replacement fluid for 24 hours; however, there were apparent changes in mixed injections containing no replacement fluids, such as Atarax-p, Bisolvon, Cepharanthin, FOY and Horizon. In Neophyllin, the solution showed a decrease in potency with the lapse of time, but was stable in prescriptions of drugs with a replacement fluid, time of 6 hours causing no change in appearance, pH, or potency.

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The quality of 3 kinds of tablets and capsules of commercial nifedipine preparations was evaluated in 5 tests: content uniformity, weight variation, disintegration, hardness and dissolution.
Following results were obtained; 1) In the weight variation test and the disintegration test, all the preparations tested met the criteria of J. P. X. 2) There was no correlation between hardness and disintegration time. 3) In the content uniformity test, the mean contents of all preparations tested were almost equal to the indicated content; however, in one preparation p-hydroxybenzoic acid derivatives added to the capsule were dissolved in the contents ana interfered with the determination of nifedipine under the analytical condition applied to the others. Consequantly, it was necessary to find another analytical condition for this preparation. 4) The dissolution ratios of 5 kinds of preparations were good, but that of one tablet showed low tendency compared with those of the others at every measurement.

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The quality of the soft capsules containing 10 mg of nifedipine in 4 brands (A to D) was studied in the tests on dissolution, weight variation, disintegration and content. Weight variation of these preparations was 1.5 to 2.8% and content was 9.86 to 10.23 mg, while disintegration time was 8.5 to 16.4 min. These results met the requirements specified in J.P. X.
In the dissolution test, nifedipine was determined by absorptiometric method. However, the standard curve was corrected due to the effect of the soft capsule itself on absorbance. In the dissolution test with use of the first fluid (disintegration, J. P. X), preparation A showed significantly more rapid dissolution time than the other preparations. A good correlation was observed between the dissolution rate and the disintegration time.
In addition, effect of pH on 50% dissolution time (T₅₀) and maximum dissolution percentage was studied. T₅₀ of preparation C was considerably influenced by pH of dissolution fluid. ut the maximum dissolution percentage of each preparation was not affected by pH. Furthermore, no significant differences were observed among the brands.

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