Vancomycin hydrochloride (VCM) has an antibacterial action against gram positive bacteria, e.g. Methicillin-resistant Staphylococcus aureus (MRSA). In the clinical setting, there are many patients who are infected with not only MRSA but also gram negative bacteria or fungi. Because VCM may also induce an adverse reaction of nephrotoxicity, we were anxious about a possible increase in nephrotoxicity due to the use of other antimicrobial agents. We thus examined the nephrotoxicity and pharmacokinetics of VCM in the rabbit and compared these findings between the rabbits administered VCM only and the rabbits administered VCM with 6 antibiotics which were found to be effective against gram negative bacteria. We found some antibiotics which lessened the nephrotoxicity of VCM and there were also other antibiotics which did not alter the nephrotoxicity of VCM. In this time, we examined the effect of antifungal agents, fluconazole (FCZ), miconazole (MCZ) and broad spectrum antibiotics, minocycline hydrochloride (MINO) on the nephrotoxicity of VCM in rabbits. As a result, an increase in the serum creatinine concentration and BUN, and morphological changes in the kidney were thus observed with VCM 300 mg/kg i.v. injection. On the other hand, the nephrotoxicity of VCM was greatly reduced by MINO, and was also dcreased a little by MCZ, but no reduction was seen by FCZ. The clearance of VCM obviously increased in the groups injected with VCM and MINO. As the renal concentrations of VCM were lower in the rabbits which were administered with VCM and MINO, MINO was suggested to decrease the uptake of VCM into nephrocytes.

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We prepared ointments containing local anesthetics (LA) with different octanol/water partition coefficient (Pc) (procaine hydrochloride (Pc: 0.02), lidocaine (Pc: 2.9) and bupivacaine hydrochloride (Pc: 27.5)) for home care patients suffering from post herpetic neuralgia. The analgesic effects of these ointments were measured in rats and healthy volunteers. Macrogol ointment (water soluble) or white petrolatum (oil soluble) was used as the ointment base.
The analgesic effects of 10% bupivacaine hydrochloride-macrogol ointment in rats were approximately 4 times that of the 2% aspirin ointment (used as a reference ointment) and were almost the same as commercially available indomethacin creams (another reference ointment). Judging from the area under the analgesic effect-time curves by 150 min after the application, the effects of procaine hydrochloride-white petrolatum were approximately 5 times that of the aspirin ointments and 1.2 times that of the indomethacin creams. The results of a test on healthy volunteers with a pain meter were also similar to those in rats. From these findings, it was thus indicated that the ointments in the combinations of LA having a high Pc value and water soluble ointment base, or LA with low Pc and oil soluble ointment base may thus be clinically useful. A good correlation was also observed between the Pc value and the analgesic effect of LA in both rats and in healthy volunteers. Furthermore, the analgesic effects in healthy volunteers also correlated well with those in rats (r=0.796 for macrogol ointment and r=0.953 for white petrolatum).

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The effect of two anti-platelet drugs, ticlopidine and dilazep, on the fetal bovine serum (FBS)-induced DNA synthesis of cultured rat renal mesangial cells was assessed by means of an [³H] thymidine incorporation assay. Each drug inhibited the 2% FBS-induced [3H] thymidine incorporation in a concentration-dependent manner, similar to the inhibition of dipyridamole. The [³H] thymidine incorporation was significantly suppressed by the treatment of more than 1 pM ticlopidine or dilazep. It was thus suggested that ticlopidine and dilazep, might prevent the progression of such glomerular diseases as proliferative glomerulonephritis, at least in part, by suppressing mesangial cell proliferation.

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Drug interaction of fleroxacin, new qunolone antibiotics, and talipexole, an antiparkinsonian drug, was studied in rats. When talipexole was administered orally before the oral administrations of fleroxacin, the plasma concentrations of fleroxacin and its metabolite, fleroxacin Noxide, decreased. The maximum plasma concentrations (C_max) of fleroxacin and fleroxacin Noxide decreased and the time needed to reach C_max.(T_max) was also delayed significantly (p< 0.05) as compared to the control. This finding suggests that the pretreatment with talipexole thus decreases the rate of absorption of fleroxacin from the gastro-intestinal tract in rats. On the other hand, when fleroxacin and talipexole were administered simultaneously, the plasma concentrations of fleroxacin and fleroxacin N-oxide increased. Regarding the absorption rate constant, the Cmax and area under the plasma concentration-time curve from 0 to 24 hours (AUC_o-24) of fleroxacin increased whereas Tm decreased significantly (p<0.05), compared to the control. Both the elimination rate constant and the Cmax of fleoxacin N-oxide also increased whereas the Tmax decreased significantly (p<0.05). The findings suggest that the simultaneous administration of talipexole increases the absorption rate of fleroxacin and may decrease the metabolism of fleroxacin to fleroxacin N-oxide.
In conclusion, the results of the present study suggest that talipexole interacts with fleroxacin in a different way than when it is administered before and/or simultaneously with the oral administration of feroxacin.

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Various dosage forms of valproic acid (VPA) prescribed for 53 child patients with epilepsy were analyzed. These patients were all given medication instructions during hospitalization at the department of Child Neurology for 21 months from 1 October 1993 to the end of June 1995. Patients less than 1 year old, who were treated with VPA, represented the largest group in our study. The prescription frequency of syrup, fine granules, long-active granules, tablets and longactive tablets in VPA dosage forms was 39, 23, 15, 15 and 8%, respectively. The selection of dosage form changed from liquid form to the powder and then to the tablet as the patient age increased. These results suggest that various dosage forms of antiepileptics such as VPA contribute to not only the pharmacotherapy of such child patients with epilepsy but also to an improvement in their quality of life.

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The in vitro antibacterial activity against Helicobacter pylori of a combination of antiulcer agents (omeprazole, lansoprazole or sodium rabeprazole) with antimicrobial agents (amoxicillin or clarithromycin) was investigated. Antiulcer agents, lansoprazole and sodium rabeprazole, thus revealed a strong antibacterial activity against H. pylori. The present study revealed an additive effect of both the proton pump inhibitors investigated in this study and clarithromycin against two standard strains and six clinical isolates of H. pylori.

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The objective of this study was to investigate the relationship between the prescription of long acting preparations and a simplification of the daily dose frequency. The medication records of 1276 patients who were treated with long acting antihypertensive medications on a once-or twice-daily regimen in November 1996 at Gifu University Hospital were reviewed. Of the 1276 patients investigated, 103 patients (8.1%) were given long acting antihypertensives alone (group A) while 1173 patients (91.9%) were given both long acting antihypertensives and other drugs (group B). The mean number of medications and the dosing regimen in group B were significantly higher compared with those in group A. Eighty-nine patients (86.4%) in group A were administered either one or multiple antihypertensives by one type of regimen. However, only 52 patients (4.4%) in group B were administered antihypertensives and concomitant drugs by one type of regimen, and 527 patients (44.9%) were administered long acting antihypertensives by daily doses in which the frequencies differed from that for concomitant drugs.
These finding suggest that the prescription of long acting preparations thus increases the probable dose frequency and complicates the dosing regimens for patients receiving both long acting preparations and concomitant drugs. Therefore, pharmacists must carefully explain to patients the difference between the medication instructions of long acting preparations and that of concomitant preparations.

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We conducted a one-month hospital pharmacy-internship for all fourth-year undergraduates (80 persons) studying at Tokushima University. The students received training on the dispensing service, the way sterilized-medications are prepared in the manufacturing laboratory, the way to prepare total parenteral nutrition, the therapeutic drug monitoring of antiepileptics, drug information, the responsibilities of the narcotic and non-narcotic drug control office and the patient care services prepared by hospital pharmacists.
Based on the results of a questionnaire survey given to the students after the training, almost all of them recognized the necessity of a hospital pharmacy-internship for one month.

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Due to the increasing number of aging patients and the number of medicines, problems continually a rise in regard to distinguishing medicines.
A survey on how patients distinguish medicine and how well they understand the directions was conducted with 51 patients taking lectures at the diabetes section of our hospital (average age 55.9+12.8, mean± SD). A survey was conducted by inquiry. Patient average eyesight was 0.8±0.4 (right eye) and 0.8±0.5 (left eye).
Whether they understood an enlarged illustration of how to remove a pill from a PTP sheet, 76.5% answered “understandable” while only 41.2% could not recognize the full-size illustration. In response to a question on the ease of reading the directions on the back of the PTP packaged tablet, 40.5% answered “easy to read” . The size of the letters they recognized as “easy to read” was 13 points or larger.
This survey revealed that almost half of the patients could not recognize medical information despite improvements of PTP packaging. Supplementary explanations and confirmations are thus necessary when giving patients dose instructions.

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In order to investigate the efficacy of pharmaceutical instruction including the instructions for use of a metered dose inhaler by inpatients with chronic bronchial asthma, intervals of hospital visits, therapeutic scores in the prescription and in the consulting room were assessed in twelve patients who were treated at Yamagata University Hospital. No patients who re-entered the hospital were recognized after their discharge from the hospital (12.8-30.4 months). The mean times of exacerbation needed for the intra-venous injection of steroids and/or aminophylline during the one year period before and after the last hospitalization in which pharmaceutical instructions were given, were 2.8 and 1.6, respectively. One of the 12 patients received the injections for treatment of asthma only one time during the one year period. In seven patients who received oral corticosteroids at discharge, three patients were able to discontinue and two patients were able to decrease their dosage. Although it was difficult to obtain any specific contribution ratio on their clinical efficacy, the pharmaceutical service including usage instruction of the metered dose inhaler by pharmacists to the patients with bronchial asthma was found to be useful especially for patients who had been repeatedly hospitalized.

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Based on information obtained through clinical pharmacy services, the patterns of side effects in individual drugs were investigated, in order to both discover and prevent side effects.
Clinical pharmacy services for the purpose of preventing hypoglycemia induced by cibenzoline, convulsions induced by levofloxacin, pseudoaldosteronism induced by kanzo, poisoning due to digoxin, and jaundice induced by ticlopidine were all herein investigated.

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Interest continues to grow regarding the influence on health of both electric fields and magnetic fields in recent years.
As a result, using a simple electric field magnetic field measuring device we measured the electric field, magnetic fields and a microwaves present inside a pharmacy.
The electric fields and magnetic fields produced by various machines inside a pharmacy need to be measured and any potential effects of such phenomena also need to be evaluated. We also need to pay attention to machines that produce other microwaves in addition to cordless telephons.

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The recent frequency of critical adverse drug reactions and the increasing consciousness of patients rights has rapidly increased the importance of drug information (DI). We as hospital pharmacists are highly responsible since we have a duty to supply the appropriate DI. From these viewpoints, we studied various methods to supply objective and high-quality DI. Before renovating our formulary, we investigated the formularies used at various university hospitals, and recognized that most disseminate basic information. We increased the number of clinical items such as the indications, side effects, and information for patients. The findings of questionnaires given to physicians suggested that they were satisfied with the contents of the new formulary and that they also wanted on-line DI delivery. We developed an on-line DI delivery system in which physicians could easily look up the newest DI when ever they ordered drugs. The maximum frequency of access to this system was 909 times in one month. Still, this system did not decrease the frequency of questions to the DI-service room, which was 156 times per month. On the other hand, it did influence the contents of questions. The questions which we could rapidly answer decreased while the questions that needed some research to answer increased. A clinical pharmacist received eight questions a month. In conclusion, we as hospital pharmacists need to revise the present DI delivery to better meet modern clinical needs. We found that pharmacists could enhance the demand and supply of DI by developing superior DI delivery systems and/or by communicating more closely with physicians.

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The and-tumor agents iphosphamide and mesna are usually separately administered for prevent injury to urinary organs like hemorrhagic cystitis and urinary disorders. Other treatments have been tried, including large-volume water intake, and urinary alkalization with sodium hydrocarbonate, etc.
We studied whether it is possible to mix 3 drugs in a bag or not, and also analyzed their stability both during and after mixing. After mixing iphosphamide, mesna and sodium hydrocarbonate, the contents of mesna and iphosphamide was found to remain at 97.8% and 97.9%, respectively, until 6 hours. However, after 24 hours, the contents of mesna decreased to 87.6%. Therefore, it was shown to be possible to use these medicines mixed in one bag by intravenous administration every 6 hours.

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