Forecast of drug demand by computer needs the following parameters such as period of order, ordering point, ordering quantity and present stock.The regular order dates are Monday and Thursday, and the maximum lead time period is four days in our hospital.Ordering point, which is the sum of a minimum possession amount and a safety surplus amount, is set as the used amount of a drug in a week, theoretically.When ordering quantity is decided, the deferred stock should be considered.Therefore, we have investigated two cases;one case is to pull deferred stock from the predicted amount, another is not.The latter case got good results, when shortage probability, ordering quantity and frequency of order were compared. Next, the problem about the shortage of space occurred for the case of transfusions, which were of great bulk, when the ordering quantity was set as the accompanying used amount of a drug in two weeks.This problem was solved by changing the ordering quantity from the used amount of a drug in two weeks to the accompanying amount of a drug in certain period obtained from the real frequency of order in the previous year.

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The serum protein binding of valproic acid (VPA) was examined with samples collected front 88 epileptic patients whose ages ranged from 3 to 78 years.Blood samples were usually collected within one to six hours after a dose in the morning.The free fraction of VPA was obtained with a microultrafiltration devices (Molcut II^®) which was developed by Nihon Millipore Ltd., Tokyo, Japan.The free and total VPA levels in serum were determined by fluorescence polarization immunoassay (TDX^®).The serum albumin levels were determined by the procedure of ionophoresis.
Total VPA levels were positively correlated with free fraction (Y=0.13X+6.39, n=88, r=0.67), and a negative correlation between serum albumin levels and free fraction of VPA (Y=-6.99X+48.49, n=88, r=0.54) was observed in the epileptic patients.We found that the serum albumin levels were decreased with the aging, and the total VPA levels were higher in younger children.The increases of free fraction in the children (8 patients in Lennox Syndrom) and the elderly (11 patients in Hypoalbuminemia) might be results from the protein binding saturation.

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For the topical treatment of postherpetic neuralgia, 8 kinds of lotions and ointments containing aspirin, anesthesin glycerin and salicylic acid, respectively, were prepared.The values of consistency and spreadability of 2% aspirin ointment preparation measured with a penetrometer and spreadmeter, respectively, were constant for 21 days when reserved at 20°C or 30°C.
Aspirin in the ointment was stable under those conditions. Among the preparations applied to the patients 2% aspirin ointment (yield value, 7000 dyn/ cm²) was suitable for topical application and most effective in respect to the pain relief. The pain started to fade within 3-5 minutes and the pain relief usually lasted for 5-7 hours.Salicylic acid ointment also afforded an analgesic effect, although the duration of the efficacy was shorter than that of the aspirin ointment.
The oral administration of aspirin and topical application of the aspirin ointment to the patients with postherpetic neuralgia showed the similar analgesic effect on arthrodynia derived from chronic articular rheumatism.From these results, the site of action of aspirin seemed to be the peripheral sensory nerve endings.

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A weight variation test, a content uniformity test, and a dissolution test were carried out, in five commercial sustained release preparations of isosorbide dinitrate (ISDN).The weight variation test and the content uniformity test with the preparations showed a small variation in each case.Their release patterns including release profile, release rate, and mean dissolution time (MDT) of ISDN were different among them.Percent of ISDN released in 8 h decreased in the following order;
Kalliant TP>Nitorol R>Helpinin-R>Frandol>Rifatac-L, and MDT increased in the same order.
Significant differences in cumulative percent of drug released were observed among some lots of Helpinin-R, Kalliant TP and Rifatac-L while no such difference was noted in Nitorol R and Frandol.

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Interaction of admixtures between bromhexine hydrochloride (BH·HCl) and 75 kinds of injections were investigated, and the molecular species of precipitate formed in the 34 kinds of admixtures were identified by instrumental analysis using IR and GC-MS.The BH·HCl injection was found to be least stable, and to undergo a variety of practically undesirable reactions as follows:
1) Precipitation of free BH and/or free acid in the admixed injection by the change in the pH of solution.
2) Precipitation of BH·HCl by the salting-out effect with Cr^- contained in the admixed injection.
3) Precipitation of less water-soluble BH·HBr by the reaction with Br^- species contained in the admixed injection.
4) Precipitation of molecular complex between BH and acid in the admixed.injection.

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To investigate a possible pharmacokinetic interaction between 4-quinolone and fenbufen, plasma concentration-time profiles and serum protein binding of norfloxacin, fenbufen and its active metabolite, felbinac, were examined in rats to which were given an intravenous dose of norfloxacin (5mg/kg), fenbufen (10mg/kg) alone or concomitantly. Although coadministered fenbufen increased the plasma elimination half-life of norfloxacin only slightly, it showed no effect on other pharmacokinetic parameters including total body clearance for norfloxacin. The extent of protein binding of norfloxacin tended to be slightly reduced by fenbufen or felbinac in vivo and in vitro. The pharmacokinetic parameters and serum protein binding of fenbufen and felbinac were not affected at all by coadministered norfloxacin. These results suggest that there may be only a minor possibility of the pharmacokinetic interaction between norfloxacin and fenbufen.

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To find out an appropriate therapeutic drug monitoring method by using saliva, we investigated the effect of four kinds of saliva stimulation methods on salivary pH, flow rate and composition in normal male subjects.Each of methods showed significantly different pH, flow rate and compositions (total protein, K⁺and creatinine levels).It was observed that the simplest method (i.e. to move mouth and tongue) had the smallest inter-individual variation of pH and relatively small inter-individual variations of total protein and Na⁺levels.In addition, this method showed no diurnal variations of pH, flow rate and compositions (total protein, Na⁺and K⁺levels). The present results suggest that to move mouth and tongue for salivation may be the simplest and most suitable stimulation method for therapeutic drug monitoring by using saliva samples. Furthermore, this method was found to be well applicable to a pilot study on the saliva to serum concentration ratio of mexiletine hydrochloride after the oral administration in normal subject.

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