We investigated the mechanism of the loss of nicardipine hydrochloride from the solutions int the intravenous delivery system.Linear relation was found between the amount of nicardipine sorbed to the administration set and the equilibrium concentration of nicardipine hydrochloride in the solution in the range of 3.0-18.0μg/ml at 30°C. The equilibrium amount of nicardipine sorbed to the administration set was influenced by the pH of the solution, and it was increased with the pH rising.Supposing that the equilibrium sorbed amount was in proportion to the apparent partition coefficients, the calculated amount of sorbed nicardipine was in good accordance with the experimental data.These results suggested that the loss of nicardipine hydrochloride in the administration set occurred through a mechanism of partition or diffusion of nicardipine to diethylhexyl phthalate (DEHP) used as a plasticizer in polyvinyl chloride of the administration set.

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Prediction of the number of outpatient prescriptions with the passage of time in an ambulatory-care pharmacy was examined. Data from our university hospital for 1989-1990 are used to predict the number of outpatient prescriptions. A simple forecasting method that provides a way for pharmacy manager and outpatients to estimate waiting time is presented.
Based on the ratio of the number of outpatient prescriptions to the number of outpatients and the coefficient of canceled appointments by outpatients and so on in each clinical department, the forecasting equations are established as follows:
ψ₁-(α_i·b-α_i·a·γ₁) ·δ₁
_??_
ψ: expected number of outpatient prescriptions with the passage of time
ψ_i: expected number of outpatient prescriptions in i-th clinical department
α_i·a: the number of outpatients in i-th clinical department at 8:30
α_i·b: the number of outpatients in i-th clinical department at 11:00 or 17:00
β: the ratio of the number of outpatient prescriptions of the all clinical departments except for clinical departments shown in table 3 (δ and γ) to that of all clinical departments
γ_i: the coefficient of canceled appointments by outpatients in i-th clinical department
δ_i: the ratio of the number of outpatient prescriptions to the number of outpatients in i-th clinical department
It is possible to estimate the number of outpatient prescriptions with the passage of time using hospital information service about the number of outpatients (α_i·a and α_i·b). First, the expected number of outpatient prescriptions was calculated by the forecasting equations at 11: 00.Secondary, the expected number of outpatient prescriptions was added a constant value depending on the number of outpatient prescription at 11: 00. For example, on Thursday, if the number of outpatient prescription (Rp.#) at 11: 00 is less than Rp.270 or more than Rp.#350, the expected number of outpatient prescriptions minus 50 or plus 50 is the final expected number of outpatient prescriptions, respectively.

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The present study was performed to estimate the efficacy of antirust and disinfection of new compounds (P1-E, P2-E, P3-E, P4-E, P2-PG1, P3-PG1, P4-PG1) as shown in Table 1 in comparison with commercial disinfectants[chlorhexidine digluconate (CHX), benzalkonium chloride (BAC) and alkyldiaminoethylglycine hydrochloride (ADE)].Antirusting effects of new compounds were evaluated by counting the numbers of rusts on the ten pins.The antirusting effects of new compounds were higher than those of CHX, BAC and ADE.Rusts were produced after 6hr in the case of BAC.Effects of new compounds and disinfectants against clinical isolated pathogenic microorganisms were determined by minimum inhibitory concentration (MIC). Antimicrobial activities of P1-E, P2-E, P3-E and P4-E were equivalent to that of BAC or ADE, while effects of disinfection of P2-PG1, P3-PG1 and P4-PG1 were higher than that of BAC or ADE.
Compatibilities of new compounds with various disinfectants or sodium lauryl sulfate (SLS) were tested in each combination.P1-E, P2-E, P3-E, P4-E and P4-PG1 had good compatibilities to the various disinfectants and the SLS in the case of each combination.These results indicated that the new compounds were very useful as antirusty disinfectants.

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The triturated mixtures of mefenamic acid (MFA) and Explotab ^® (EX) were prepared by means of powder/powder mixing technique.After storage under reduced pressure at 60°C for 5 hr, with scanning electron microscopy, it seemed likely that EX was transformed to a porous powder.The crystal peaks of MFA by X-ray diffraction had almost disappeared.The dissolution profiles of MFA from the triturated mixtures stored under reduced pressure at 60°C for 5 hr were enhanced in comparison with that from a freshly prerared mixture.With the increase of either the storage temperature or the time under reduced pressure, the particle size of MFA tended to increase on the surface of EX, and MFA also tended to peel from the surface of EX.Consequently, the crystallization of MFA was accelerated.

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For the beginning of the patient compliance of instructions given by pharmacists in the children's ward, the study of drugs used and the awareness of the doctors were investigated.In the surveillance of drugs used, all prescriptions (8084 pieces) and request sheets for injections (2964 pieces) from January to December in 1990 were investigated.The amounts of antitussive drugs, antiepileptics, antibiotics, drugs for controlling intestinal function, cardiotonics and diuretics used were large as compared to the other drug groups.In the monthly accounting of the amounts of antitussive drug and antibiotics used, the amounts used were larger in March and July than those in the other months.In the surveillance of dosage forms, the percentage of powders and solutions was over 50%.
In the awareness of doctors, the subjects were 15 pediatricians.Though the instruction by doctors was widely done, not only the patients and their families but also the doctors were unsatisfied with the results.The patient compliance of instruction by the doctor tended to decrease after leaving the hospital and outpatient clinic.The pertinent instruction by the pharmacists according to this study and their awareness were welcomed by the patients, their families and doctors.

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The discrimination of drugs is a very important pharmacist's role in the hospital pharmaceutical practice.At present, however, it is extremely difficult to analyze the ingredients of a mixed powder accurately, except the case that a drug in the mixed powder is deduced from its characteristic odor or taste and/or color, in the routine DI and dispensing services. In this paper, the analysis of the ingredients in a mixed powder was studied by the use of X-ray powder diffraction.Ingredients in the mixed powder were identified by comparing the intensity and the number of observed diffraction peaks to the corresponding peaks of the standard substances and by subtracting successively the peaks of the identified ingredient from the whole peaks of the mixture.Three kinds of original data bases such as the powdered organic and inorganic drugs, the powder or fine granule of organic drugs were constructed in order to apply the X-ray powder diffractometry for identification of the drugs.
In general, a thinner sample is preferred for X-ray powder diffractometry.However, the sample about 0.5mm in thickness was found to be well suitable for the identification of the ingredients of the mixed powder.The ingredients of the mixture consisting of one to three kinds of organic drugs were completely identified.In the mixture of four kinds of organic drugs, three ingredients could be identified, but the residual ingredient was not always identified depending on the mixing ratio.Each ingredient of the inorganic mixture was analyzed in a similar manner as that for the organic mixture.
The time required for measurement was 30min, and the time for analysis was about 30 sec, so this X-ray powder diffractometry is very useful and applicable to the routine DI and dispensing services in a hospital pharmacy.

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A simple HPLC method for the determination of zonisamide in serum for the pretreatment with methyl alcohol is reported.A reversed phase column (Yanapack ODS-A) was used and the mobile phase consisted of a mixture of 50 mM ammonium acetate and methyl alcohol (2: 1). Furosemide was used as an internal standard.Linear relationship between zonisamide levels in serum and peak area ratio (zonisamide/internal standard) was observed in the range of 1-40μg/ml.Ethosuximide peak was close to zonisamide peak.Simultaneous administration of ethosuximide and zonisamide was thought to be very rare, therefore, the serum level of zonisamide could be determined with this procedure.The serum zonisamide level of patients treated with zonisamide and other antiepileptics (phenytoin, carbamazepine, valproic acid) was lower than that of patients treated with monotherapy of zonisamide.

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We prepared two classes of PDI of different preciseness for each group of antihypertensive drugs on trial: a brief PDI containing actions and effects, brief precautions with a few side effects and a precise PDI containing actions and effects, how to use, precautions and moderately precise side effects.Patients prescribed with one of the antihypertensive drugs were given one of the two classes of PDI and were asked to answer a questionaire at the next visit after two to four weeks.Of the 265 patients who answered the questionaire, 166 were given brief PDIs and 99 were given precise PDIs. 60% of the patients answered “I read the PDI well”, 70% answered “I could understand the actions and effects well”, 71% answered “PDI was useful” .Of 93 patients who had not used drugs completely before, 34% answered that they had come to take drugs more completely after reading the PDI: 55% of the patients for the precise PDI and 24% for the brief one (p<0.01). Description of side effects made 57% of the patients satisfied while 10% of the patients were anxious: 4% for the brief PDI and 20% for the precise one (p<0.05).
This survey suggests that precise PDI with moderate preciseness of side effects makes patients anxious a little, but it makes them rather compliant than noncompliant.From these trial, PDIs were read well and were shown to be usefull using especially the precise ones.

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The statistics indicates that the constitution of children, which includes height and body weight, has developed during the last 40 years.Therefore, we investigated that body surface area of children at present for every age which was calculated with Fujimoto's formula was greater than that in 1948.So we reexamined pediatric dose obtained from Augsberger's I, Augsberger's II, Young's, and Fujimoto's formula.The pediatric dose ratio based on body surface area in 1948 much more corresponded with the dose ratio obtained from the Augsberger's II formula.On the other hand, the pediatric dose ratio based on body surface area for every age in 1987 was shifted to higher dose ratio compared with that obtained from the Augsberger's II formula. The pediatric dose ratios obtained from three formulas except Fujimoto's formula indicated lower dose ratio than that obtained from Fujimoto's formula.Furthermore, under the age of five, pediatric dose ratio calculated from Fujimoto's formula was higher than that calculated from Du Bois's formula.The difference between the two dose ratios was larger as the age of children was lower.Consequently, considering big change in the constitution of children during the last 40 years, there may be a possibility to estimate lower pediatric dose than the dose which was required in the present children, if the pediatric dose was eviluated with Augsberger's II formula.

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Dissolution profiles of a few sustained release preparations containing β-blockers were examined in media of various pH.Dissolution patterns of carteolol from Mikelan-LA tablets were found to be independent of pH values of media, while those from sustained release products containing pindolol depended on pH values of media.The latters consisted of pH-independent fast dissolving part and pH-dependent sustained release part.There were also difference in dissolution rates among brands.
In Blocklin-L capsule, apparent dissolution rates of pindolol at pH 5.0-6.0 exceeded those atthe first and second dissolution media of JP XII when UV absorbance was measured.Its dissolution rates measured by HPLC were found to be smaller than those measured by UV absorbance. Some material (s) was likely to be dissolved in dissolution media from capsule ingredients which exhibited UV absorption only at pH 5.0-6.0.

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We prepared a new type of medicine diary in which inpatients should fill their conditions by themselves.We delivered these diaries to inpatients, who were hospitalized in the Second Department of Surgery and the First Department of Internal Medicine, and examined the matters filled in these diaries.As the results of discussion on its usefulness, the followings were obtained.
1) The inpatient medicine diary clearly reflected the number of drugs administered and the frequency of changing prescription, which suggested the usefulness.
2) The inpatient medicine diary reflected increase and decrease in the amount of drugs administered and withdrawal of administration rightfully and with real time.This suggests that it should be a quite useful method for us to give the instructions efficiently.
3) The inpatient medicine diary is effective and useful in making up good communication with patients.

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Fragmin IV, dalteparin sodium for injection (1000 international units/ml), was studied on its compatibility with various transfusions and vitamin injections.Every combination showed neither change in external appearance and pH nor significant decrease in residual anti-factor Xa activity up to 24 hours after mixing.Fragmin IV, so compatible with various transfusions and vitamin injections, is believed to be practically useful for treatment of disseminated intravascular coagulation (DIC).

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We investigated quantity of antibiotics used for injection and the changes of clinically isolated microorganisms during the period from April 1986 to September 1990 at Shinshu University Hospital.The aim of this study was to clarify the relationship between occurrence of drug resistant bacteria and quantity of antibiotics-injection used.It was found that 1) the number of clinically isolated Staphylococci has been increasing year by year, 2) the 3rd generation cephalosporins were the most used agents among the antibiotics during these period, 3) frequency of isolation of Staphylococci was recognized to be relatively high at the clinical area where the 3rd generation cephalosporins were consumed in large quantities.

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Symmetrel (Amantadine hydrochloride) has pharmacological actions as both anti-Parkinsonism and antiviral drugs, however, it is used only as an anti-Parkinsonism drug in Japan. In this report, we surveyed the frequency of fever caused by influenza for the patients in hospital from November 1989 to March 1990 and assessed the relationship between the reduction in fever and taking Symmetrel.The fever caused by influenza was significantly reduced by taking Symmetrel.In the period from the end of November 1989 to the end of January 1990, in which the influenza A Hong-Kong was raging throughout Aichi Prefecture, the fever was more significantly reduced by taking Symmetrel than that in total period.

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A plastic bag, which is composed of 3 layers i.e.polypropyrene, nylon and polyester films, has been devised for sterilization of liquid preparations for external use by an autoclave.Physico-chemical tests such as heavy metal, nonvolatile residue and water vapor permeation were carried out to evaluate the suitability as a container for liquid preparations.The adsorption of chlorhexidine gluconate and benzalkonium chloride from aqueous solutions to the plastic bag was investigated.
This bag was adopted for the requirements under physico-chemical tests for plastics.There was no decrease of chlorhexidine gluconate or benzalkonium chloride by adsorption to the plastic bag under autoclaving at 115°C for 30min, and subsequent storage at room temperature for 4 weeks.It was suggested that the newly-devised plastic bag was very useful for sterilization of liquid preparations in hospital pharmacy.

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Human antithrombin III (AT III) products have been developed by two companies, Green Cross Co.Ltd.and Hoechst Japan in Japan.These two companies have recently modified the purification methods for AT III.New products from Green Cross and Hoechst Japan had 1.7-f old and 1.9-fold higher activities than the old type products, respectively.A single band was observed by SDS-polyacrylamide gel electrophoresis, and its molecular weight was evaluated to be about 63, 000 daltons.Two bands were detected by isoelectric focusing, and the isoelectric point of the major band was about 5.10.On the other hand, two peaks were observed in the old AT III product from Green Cross by use of high-performance liquid chromatography.The molecular weight of the major peak was approximately 60, 000 daltons, while that of the minor peak was about 159, 000 daltons.The precipitation of the AT III products indicated completeidentity by the double immunodiffusion assay.From these results, the quality of the new AT III products from both manufacturers were confirmed to be improved.

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