A high-performance liquid chromatography (HPLC) assay was developed for the determination of tosufloxacin in plasma. The plasma samples were directly introduced onto a HPLC precolumn, or after filtering through a Molcut II^® membrane filter, which prolonged the life time of the precolumn resulting from the removal high molecular proteins. The tosufloxacin and sparfloxacin as an internal standard in plasma or filtrate were separated from any interfering substances and then were concentrated on a pre-column using as ODS stationary phase and then were introduced to an analytical column with an ODS stationary phase by column switching. Tosufloxacin and sparfloxacin were detected by ultraviolet absorption at 269 nm. The determination of tosufloxacin was possible over the concentration range of 50-1500 ng/mL; and the limit of detection was 20 ng/mL. The recovery of tosufloxacin added to plasma was 96.2-99.5% with a coefficient of variation of less than 1.9%. This method is applicable to drug level monitoring in the plasma of patients being treated with tosufloxacin and in healthy volunteers participating in a scientific investigation to analyze the pharmacokinetics of drug-drug interaction of tosufloxacin.

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We examined the pharmacokinetics of theophylline in two types of experimental diabetic rats, streptozotocin-induced diabetic (STZ) rats with insulin dependent diabetes mellitus, and a genetic model of non-obese Goto-Kakizaki (GK) rats with non insulin dependent diabetes mellitus. After the rats were administered theophylline either intravenously or orally plasma was taken for a pharmacokinetic study. There were no significant differences in the pharmacokinetics of theophylline in the STZ rats compared with those of the controls. On the other hand, a delayed elimination process and absorption rate of theophylline were observed in GK rats in comparison to those of the controls. There findings suggest that two different phamacokinetics of theophylline exist depending on the two types of diabetic rats.

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Abstract-Vancomycin hydrochloride (VCM) has a potent bactericidal activity against Gram positive bacteria, especially, Methicillin-resistant Staphylococcus aureus (MRSA). In the clinical situation, patients infected with not only with MRSA, but also with Gram negative bacterium or fungi are encountered. Because VCM has an adverse reaction of nephrotoxicity, we examined the nephrotoxicity and drug interactions of VCM and some antibiotics and antifungus agents in rabbits. We have already reported on the attenuation of nephrotoxicity by VCM with imipenem/cilastatin sodium, flomoxef sodium, fosfomycin sodium or minocycline hydrochloride, but no attenuation with ceftazidime, cefpimizole sodium or fluconazol. In this study, we investigated the renal function and VCM clearance in MRSA-infected patients, and compared our findings with those in the patients coadministered antimicrobial agents which decreased the nephrotoxicity of VCM in rabbits (decreasing group, n=23) and the patients coadministered the drugs which didn't decrease the nephrotoxicity in rabbits or administered VCM alone (non-decreasing group, n=22). No significant differences were observed regarding age, serum creatinine, BUN, serum potassium, total protein, albumin, WBC and CRP at the starting time of VCM-treatment, VCM doses, period of VCM treatment, and serum VCM concentrations (peak, trough) between the decreasing group and the non-decreasing group. However, the serum creatinine levels in the nondecreasing group were significantly higher than those of the decreasing group at 2 weeks after the VCM theatment. In addition, the serum creatinine levels at the end of the VCM treatment in the non-decreasing group were higher than those of the dereasing group.
However, no significant differences were observed in the VCM clearance and BUN between the decreasing group and the non-decreasing group, even though the serum creatinine in the nondecreasing group significantly increased. The high ratio of cancer in our patients (decreasing group n=12, non-decreasing group n=15) may have influenced our resuls. Further investigations are needed to estimate whether or not antimicrobial agents may influence the renal functions in VCM administered patients.

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Topical medicinal substances (or drugs) in liquid formulations are conventionally applied using cotton, gauze, or other applicators that are made of cellulose materials. Thp adsorption of drugs to these cellulose materials is known to reduce both drug availability and efficacy in patient treatment.
In our previous studies, cellulose fibers were reported to be negatively charged due to the presence of a bleaching process. Substantial adsorption of positively charged cationic drugs, such as disinfectants, due to electrostatic interaction has been observed. The objective of this study was to compare three typical bleaching agents, namely sodium hypochlorite, sodium chlorite and hydrogen peroxide, in organic acid (R-COOH) generation and drug adsorption for cotton, with the goal of selecting the most suitable bleaching agent for bleaching cotton.
The results indicated that hydrogen peroxide generated less organic acid than the other two agents. Consequently, the cationic drug adsorption to the cotton bleached by hydrogen peroxide was the lowest. In addition, no visible differences were seen in the whiteness for the cotton bleached by these three agents. Therefore, the use of hydrogen peroxide is recommended as the bleaching agent for cotton.

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The infection with hepatitis B virus (HBV) has long been a problem in the multiusage of injectable drug solutions with the contamination of HBV. However, there is still no experimental evidence of an infection by HBV blood cross contamination, except for epidemiological analyses. Moreover, the stability of HBV antigen and HBV-DNA contents in injectable drug solutions has not yet been analyzed. Therefore, the stability of HBV antigen and HBV-DNA in injectable drug solution (saline, heparin, 1% lidocaine, 1% heparin in saline) for 7 days under 4°C after dilution of HBe positive patients serum with each solution was investigated in this study. The HBe antigen and HBV-DNA contents showed no decrease for 7 days. Although the relationship between HBe antigen or HBV-DNA and infection ability, has yet to be elucidated, that drawing blood from an HBV carrier clearly requires extreme care.

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In the intensive care unit (ICU) for critical care, there is a high incidence of methicillin resistant Staphylococcus aureus (MRSA) outbreaks by cross infection when MRSA carriers happen to be in the ICU. A hospital infection of MRSA causes particular problems because of the high cost of treatment and prophylaxis. We examined the effects of mupirocin calcium hydrate nasal ointment (MUP) to eliminate MRSA infection by applying it to all patients who were admitted to our critical care ward. During the study period, a historical control phase, a placebo-controlled phase (phase-I) and a phase for blanket use of MUP (phase-II) lasted 4, 8, and 4 months, respectively. A significantly lower rate of MRSA infection in the group using MUP (n=243) was noted in comparison with the historical control group (n=121) (0.4% and 6.6% respectively; p=0.0110). In phase-I, only one MRSA infection was documented in the MUP group compared to 7 in the placebo group (p=0.025). An analysis of the costs showed a significant difference in the average cost of the drugs for MRSA infection per patient in the historical control period and phase-II (¥14, 698 and ¥376 respectively; p<0.0001). In conclusion, nasal decontamination using MUP on admission to the ICU for critical care was found to be effective in eliminating MRSA infections. In addition, this regimen was considered to be a cost-effective solution for the MRSA problem because of the significant reduction in the drug cost for MRSA infection.

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Patient compliance is an important part of drug therapy, but not all patients take their medication exactly as directed. Although it is very important to investigate and identify factors that contribute to poor compliance, there have so far been very few studies of this kind in Japan. We therefore performed a cross-sectional study to analyze the factors associated with poor patient compliance (various patient background factors and a dozen matters dealing with medical care: the relationship between physicians and hospital staff, the time required to visit hospital, the drug therapy regimen, etc.) using the data obtained from patients who had been subjects of a QOL study on Carvedilol.
The results showed that patient compliance was “good” is 83.3% of the patients, and that compliance was poorer among the following three groups of patients: employed patients (odds ratio: 5.15, 95% confidence level: 1.53-17.30, p=0.01), female patients (odds ratio: 3.39, 95% confidence level: 1.07-10.74, p=0.038), and patients who felt that their attending physicians did not provide enough information about the administered drug (odds ratio: 2.58, 95% confidence level: 0.88-7.58, p=0.084).

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The effect of albumin and α₁ acid-glycoprotein (AAG) on the binding of cibenzoline was studied using the pH 7.4 phosphate buffer (PBs) and human plasma. The binding in 40 inpatients who received cibenzoline therapy was measured. The cibenzoline concentrations of samples were measured by high performance liquid chromatography. As a result, not only the PBs but also human plasma samples the binding increased in propotion as the concentrations of albumin and AAG increased. On the other hard the binding decreased in inverse proportion as the total cibenzoline concentration increased. However, in the patient samples the effect of the total concentration of cibenzoline and the concentrations of albumin and AAG on the binding was slight and the mean binding ratio was about 80%. These results suggest that when clinically monitoring the cibenzoline blood concentration in clinical monitoring the total concentrations of cibenzoline alone appears to be sufficient.

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Japanese Good Clinical Practices (GCP) guide, which was based on ICH-GCP, was revised in April 1998. Pharmacists must manage clinical trials under conditions that are in compliance with the GCP. We reviewed the clinical trials performed in our hospital using a questionnaire, regarding the monitoring and auditing system of these trials by sponsors. It was recognized that about 90% of sponsors had staff education and training programs on monitoring and auditing. In addition, most sponsor desired that the protocols are being followed by the support of clinical research coordinator (CRC), and thus cooperate to direct access to source data/document and transcribe such information onto the case report forms. These results may be useful to improve the quality and integrity of the data from clinical trials in our hospital. We consider it very important for each institutional administrator to understand the sponsor's view.

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The rapid growth of pharmaceutical care in Japan has resulted in the need for a new clinical support system for drug information (DI) services. The DI committee of the Kanagawa Society of Hospital Pharmacists conducted a survey of hospitals in 1997-1998. The purpose of the survey was to determine such things as the number of pharmacists actually working in DI, the number of hospitals publishing a DI newsletter and also the number of hospitals utilizing computer automation in their DI programs. The survey consisted of 16 questions that were mailed to 353 hospital pharmacies, out of which 155 responses were returned. The results of the survey were compared to the findings of a similar study performed in 1996. One hundred-two of the 155 pharmacies (66%) indicated that they had a DI-room within their facility. Eighty-five percent of the facilities had their own hospital formulary. In addition many (56.8%) of the DI-rooms had a computer system, but on the other hand only 11.0% of all institutions used it for computer communication and literature seachs such as for MEDLINE. As changes occur in the medical environment, the DI related job should respond accordingly. An average citizen can now access much DI through the Internet, but the qualify of that information may be suspect. The problem today is how to encourage the hospital pharmacies to also access the Internet and both use and evaluate the huge amount of DI that is to be found there.

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We examined that the influences of pre-treatment with the peroral intestinal irrigator (Niflec^®) for the 69 post-operative patients of colon cancer from June 1995 to June 1997.
Number of irrigation methods have been increasing administrated at the Takarazuka City Hos-pital since 1995. The Niflec^® irrigator was used for the 39 patients.
In the patient group, in which such these irrigator were used, the administrative periods of theantibiotics significantly decreased. On the other hand, the hospital-stay of the these patients alsoshorted.
In our investigation, the 1st and 2nd generation cephems were considered to be the first choicein post-operative infection control. Those drugs were thus used as the antibiotics of choice forthe infection control according to the species of the bacterium and their amounts. MRSAs wasnot detected.
The results obtained from this survey suggest that pre-treatment of patients with a peroral in-testinal irrigator is therefore an effective treatment for post-operative infection control.

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In september 1997 the Ministry of Health and Welfare started to require the documentation and management of blood formulations in each medical facility, investigated all blood formulations in use. These blood formulations included the products of blood transfusion and plasma fractionation. Our Department manages the plasma fractionation products while the rest are controlled by the Division of Transfusion in Clinical Laboratory Department.
This report was concerned about the documentation and management of plasma fractionation products using an original personal computer program developed in our Department. The outstanding characteristics of the management were the use of our original number, to name the individual products and each product never applied to different patients. A follow-up study of the management for about one year was carried out and the oversight by medical staff in each clinic was 2.1%(165/7, 752). The particular follow-up and training for medical members were performed by pharmacists and the omission was decreased from 165 to 20, thus resalting in 0.2%.
For the rational use and management of plasma fractionation products, the role of pharmacists is therefore considered to be important and indispensable.

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In order to treat psoriasis, many kinds of drugs are administered systemically and topically. However, the topical admimistration of drugs is preferred to the systemic administration because the former can occasionally cause serious side effects. Zinc Pyrithione (ZPT), which is recognized as an active ingredient in a major anti-dandruff shampoo, was introduced as a new antipsoriatic agent. In this study, ZPT lotions as a hospital preparation were prepared for topical administration.
Hydroxypropylcellulose-H (HPC), sodium-polyacrylate (PANA) and carmellose sodium (CMC) were used as a suspending agent of 0.5% ZPT lotion. The following physical characteristics, the viscosity, the osmotic pressure, the sedimentation, the microscopic view and the dispersion were investigated in each ZPT lotion containing different suspended agents.
The viscosity of the ZPT lotion with HPC and CMC increased with the additive ratio of these suspended agents. On the other hand, the viscosity of the ZPT lotion with PANA increased logarithmically with its additive ratio. The low osmotic pressure of each lotion was expected to be less irritable in clinical application. When ZPT lotions were stored at room temperature for 14 days, the lotion with HPC or CMC showed free sedimentation and caking of the particles. In contrast, the lotion with PANA showed a growth of particles by a microscopic analysis and coagulated sedimentation by macroscopy. These phenomena may be due to the ionic intensity of the solution and the interaction between ZPT particles. The dispersion time of ZPT lotions with PANA was shorter than those with HPC or CMC.
Based on our findings, 0.2% PANA was found to be preferable to HPC and CMC as the suspended agent in ZPT lotion.

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Drug information for every outpatient was made for clinical use. Referring to about 900 prescription drugs, the name, effect, precautions for use, and contraindications for concomitant use for each drug were stated within 250 characters on both pages of a sheet of paper measuring 5.0cm×10.5cm in size.
After starting this system the number of requests for supply of the drug information was about 6200 per month on the average, 49% of the total prescription number. This is a system that can be taken up by every hospital, as this system it does not require either any special instruments, special pharmacists or any prolonged waiting time for the patients to receive their drugs. Questionnairing to the patients showed the informating to be sufficiently understandable, thus improving the patients' knowledge of the drugs. Furthermore, 45% of the patients answered that they began to take drugs in a proper way thanks to the additional information. This drug information system was thus found to successsfully improve the QOL of the patient.

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Switch OTC preparations of H₂-receptor antagonists have been marketed since September 1997, which causes concern about the possible concomitant use with H₂-receptor antagonists while the patient does not know that they are from the same drug class.
We conducted a telephone-interview survey of patients awareness of drug information leaflets on switch OTC preparations of H₂-receptor antagonists including precautions for use and adverse drug reactions in 203 patients who were taking ranitidine.
Of the 203 patients, 16 (7.9%) purchased OTC preparations including cold remedy and gastric drugs. Of the 203 patients, 164 (80.8%) replied that they did not know about the selling of switch OTC preparations, because, for example, they were aware of their commercial message but did not know that they were from the same class of drug as ranitidine.
Twenty-three (11.3%) of the 203 patients also received medication from other hospital (s), although type of drugs were not known.

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Kanebo Memorial Hospital has been engaged in the establishment of its original computer system since relatively early days. The pharmacy operation system, which organically connects the functions assisting the pharmacy operations and medical services, has been developed as a part of the integrated institutional system for the purpose of providing the patients with a better clinical environments. Recently, the hospital's original drug information supply system for outpatients was established. This drug information supply system, by programming the system on the host computer and by keeping the database of the drug information on the host computer, enables the users to directly use the data on the patients stored on the host computer and issue the Drug Information Sheet without reentering the necessary information such as the name of the patients, specialty or prescription details. Direct data processing and printing operations on the host computerenable the users to print the Drug Information Sheet quickly, and the users could thus issue 400 to 500 sheets even on the busiest days without having any frustration. The system is designed to print the sheet by grouping the information on the drugs which are put into the same bag so that it is easy for the patients to concurrently check and receive the drugs and the drug information in the bag. Another merit of this system is that the users can switch the information for different specialists that the information specific to the specialty can be retrieved in the case of the drugs used for different indications in different specialties. The trial use of such centrally managed information on the host computer like this system established by Kanebo Memorial Hospital may thus help medical professionals to cope with providing drug information to individual patient.

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The on-line drug information retrieval system in which databases such as a package insert database, medication history database, instruction of medication database, product identification database, and so are linked together was developed. Each database was linked to each other through a drug code number. The pharmacist who is responsible for drug information services updates the information in the database with latest information every day. Various type of information on the targeted drug can be obtained from multiple databases by this system. The operation processes were programmed, and this system can be utilized on several computers connected with LAN in the pharmacy department. As a result, every pharmacist in our hospital can use this system easily. Pharmacists utilize this system to confirm the latest information written in the package insert, the preparation of the drug information provided to the patient, product identification, and so on.
Using this system, pharmacists can retrieve the latest drug information and provide to the pharmacotherapy running at present. This system is therefore considered to be useful for the rational use of medication.

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We studied the effect of a patient forgetting to take acarbose and also investigated whether there is any benefit in taking it within certain time periods after a meal. The subjects consisted of 10 volunteers and the tests were conducted during lunch periods. Over 6 test days the subjects ingested breakfast (100 kcal; carbohydrate 78%) and lunch (624 kcal; carbohydrate 56%) each day. On the first test day, as a control, no acarbose was given. Blood was drawn 7 times to determine the levels of plasma glucose and immunoreactive insulin (IRI) (just before and after a meal, and after 30 minutes, 45 minutes and 60 minutes, 90 minutes, and 120 minutes after a meal). The same 10 subjects then took 100 mg of acarbose just before a meal, and 30 minutes, 45 minutes and 60 minutes after starting a meal respectively on different days. The levels of plasma glucose and IRI were measured for the 7 blood drawing times. The levels of plasma glucose of the subjects who took acarbose just before a meal were significantly lower at the 5 times, from just after meal to 90 minutes after starting time of a meal, compared to the controls. The levels of IRI in the subjects who took acarbose just before meals were lower at all times compared to the controls and other intakes. There was no significant difference in the area under the blood concentration-time curve (AUC_0-120) 1of plasma glucose during the 120 minute period after starting a meal between the subjects who took acarbose just before a meal, just after starting a meal, and 30 minutes after starting a meal. It was found that taking acarbose was therefore the most effecctive just before a meal but, if this is forgotten, it can still be effective if taken 15-30 minutes after starting a meal.

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Prednisolone (40 mg/day) and cyclosporin A (200 mg/day) were administrated in a patient suspected of suffering from Polyarteritis nodosa. To avoid steroidal side effects, the prednisolone dose decreased to 20-40mg every other day. Since the cyclosporin A trough concentration was high (310ng/ml) for a dose of 200 mg/day, the dose was decreased to 100 mg/day. The patient complained of severe numbness in her left leg and hands and a decreased grasping power while taking the reduced doses, and her trough levels of cyclosporin A was 30.0-46.8 ng/ml. When the cyclosporin A dose was increased to 150 mg/day, the patient's numbness in her left leg and her grasping power improved, and her cyclosporin A trough level was 71-86.3 ng/ml. The prednisolone dose was not changed while the dose of cyclosporin A was increased. There were no serious side effects while administration of cyclosporin A. These findings suggested that coadministered cyclosporin helps to decrease the occurrence of numbness and while also improving the grasping power in patients suspected of suffering from Polyarteritis nodosa who receiving steroid therapy.

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