Glutathione (GSH) was combined with trace elements in infusion solution for total parenteral nutrition.The effects of the trace elements (copper, zinc and selenium) on the stability of GSH, and the stabilization of GSH by protamine sulfate (PT) and ascorbic acid (AC) were studied by reversed-phase high-perfomance liquid chromatography using 4-(amino-sulfonyl)-7-fluoro-2, 1, 3-benzoxadiazole (ABD-F).The contents of GSH decreased in the presence of zinc, copper, and selenium, in that order.In particular, 14%of GSH remained after 10 minutes at 25°Cin the presence of 5μM of selenium.The contents of GSH decreased with an increase in the concentration of selenium.GSH was stabilized by PT or AC in the presence of trace element.When 5μM of cupric sulfate was added to the GSH solution after 20 minutes, 39.5% of GSH remained.On the other hand, 70.6% of GSH remained under the same conditions in the presence of 10mg of AC per ml.

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Frequency of the prescriptions of Chinese herbal extract remedies by each department and classification of the usages were studied among the prescriptions having been issued during June 1 to 30, 1988, for outpatients and innerpatients at Teikyo University Hospital.Its ratio to the total number of the prescriptions was 3%, of which 30% was of Shosaikoto.It was found that Shosaikoto was used primarily for the treatment of chronic hepatitis.Contents of amino acids, Na and K in frequently used Shosaikoto of different companies were analyzed and the values obtained exhibited variations.

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There are some cases that half life of digoxin is prolonged in elderly patients (elder than 60 years old), although serum creatinine (Scr) and serum urea nitrogen (SUN) levels are within normal range [Scr (<1.2) and SUN (<20)].The half life of digoxin in patients over 60 years old (71.6±23.2hr, n=8) was significantly longer than those in other patients (47.4±18.9hr, n=16) (p<0.05) in comparing among patients within normal Scr range.Among the elder age group, the half life in normal Scr group was 71.6±23.2hr (n=8), whereas that in abnormal Scr group tended to be prolonged to 84.4±41.8hr (n=27).In four cases where Scr is 0.3, 0.9, 1.1 and 1.4 mg/dl, the half life of digoxin calculated based on creatinine clearance that was estimated by urinary creatinine, urine volume and body surface area (2.88±0.42 day) was significantly shorter than that obtained from the serum digoxin concentrations measured at two points or more (3.65±0.37 day) (p<0.01).
These findings suggest that it is desirable to control the serum digoxin by measuring its level routinely for a better digoxin therapy in the elderly patients, since the index of elimination rate constant or the half life calculated by Scr and/or SUN might be less reliable and utilization of CLcr might be also less suitable in some cases.

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As to evaluating fibrinolytic activity of urokinase, microcalorimetric method was attempted. We could find that thermal reaction is very useful to evaluate the fibrinolytic activity of urokinase, by using plasminogen as the substrate of urokinase and fibrinogen as the substrate of plasmin.

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The photostability of nifedipine (NP) was studied in heterogeneous solid-state preparations. Two kinds of powders, obtained by crushing tablets, granule and fine-granule which were commerced on Japanese market, were subjected to the test, and their photostabilities of NP were compared with that of NP in standard sample (control).The protective effect of packaging with colored glassine-paper on photodegradation of NP was also examined.The preparation samples were exposed to normal room light, fluorescent lamp and day light, under the conditions of 750 lux of average irradiation and 35% of relative humidity at ambient for 720 hours. Changes of amount of NP, its nitroso-derivative and nitro-derivative were determined with highperformance liquid chromatography (HPLC).
NP in each preparation which was packaged with white glassine-paper decomposed rapidly after exposure to light, according to pseudo first-order kinetics.The result of regression analysis suggested that NP of two kinds of powders, granule and fine-granule decomposed completely in about 120 hours.However, the amount of NP in control was maintained above 65% of the original potency for 120 hours after exposure to light when it was packaged with red glassinepaper. From the relationship between photodegradation rate constants and area under the transmission curves of various colored glassine-papers, the range of wavelength between 300nm and 460nm may relate to the decomposition of NP.Furthermore, two unknown peaks which increased after exposure to light were observed on HPLC chromatogram of NP.

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Although Enoxacin (ENX) tablet is a film-coated tablet with protection from light, it is often administered after grinding the tablets.In the present study, therefore, its stability after grinding was evaluated.After grinding the tablets, the particles were packed by using two different types of wrapping papers, and stored under three different conditions i.e.with protection from light at room temperature, at 30°C and 92% of relative humidity (RH), and with illumination by fluorescent light (800 lx) at room temperature.After the storage, the observation of appearances, the measurement of hygroscopic degree, and the measurement of ENX content and the identification and quantification of decomposition products by high-performance liquid chromatography (HPLC) were undertaken.
The results revealed that there was no decline in the content of ENX under any conditions adopted for storage, except that some changes were found in color shade of the sample stored with illumination by fluorescent light at room temperature, together with formation of two kinds of decomposition products, and that weight gain by 8-10% due to hygroscopicity was noted after storage at 30°C and 92% RH.From these findings, it was concluded that ENX tablet after grinding should be stored with protection from humidity and light.

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Protective effect of polyethylene telephthalate (PET) film was studied, using Methylcobalamin (CH₃·B₁₂) and Furosemide which were unstable under the photoradiation. CH₃·B₁₂ was mixed in the 5% glucose solution and dript (2.8ml/min) from the plabottle setted for transfusion under fluorescent lamps, where the illuminance at the top of the bottle was 1, 000 lux in a laboratory or a ward. When dripping and irradiation started simultaneously, no CH₃·B₁₂ could be detected in the drops 30 min later; whereas 75% and 50% of CH₃·B₁₂ were found after 30 and 120 min respectively, when plabottle was shielded with PET film.
This protective effect was observed in a ward as well. Further experiment without dripping showed that CH₃·B₁₂ was linearly degraded with time by irradiation, and about 80% of it remained after 60 min when plabottle was shielded with PET film; whereas 45 and 20% of CH₃·B₁₂ remained after 5 and 10 min, respectively when PET film was not used. These data indicated that the rate costant of photogradation of CH₃·B₁₂ in plabottle shielded with PET film was less than 1/40 of that without PET film.Moreover, furosemide in plabottle shielded with PET film was not almost photodegraded after irradiation for 4hr under sunlight, but not detected when no PET film was used. These results indicate that PET film was clinically very useful for the protection against the photodegradation of CH₃·B₁₂ or furosemide in plabottle for transfusion.

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