Although clinical pharmacists participate in delivering safe and effective drug therapy to individual patients, there has so far been little assessment of the importance and quality of clinical pharmacy services. Physicians need drug information in order to practice safe and effective drug therapy. Previously, pharmacists provided drug information to physicians at the drug information section of the hospital pharmacy. At present, clinical pharmacists in most hospitals consult with patients regarding the drug therapy, and sometimes recommend the dosage regimen and provide drug information regarding the drug therapy to the physicians directly. We analyzed the records providing drug information to physicians and clinical interventions from March through May in 2002, and evaluated the acceptance ratio of pharmacists' recommendation for drug therapy. Clinical interventions included advice regarding drug therapy and pointing out prescription errors, inappropriate dosage, adverse drug reactions, drug interactions, and other aspects. In our survey, 73.8% of all interventions by the pharmacists were accepted by the physicians. For advice based on therapeutic drug monitoring, pharmacokinetics, laboratory data, and medication history, the interventions had a high probability of being accepted by physicians. Since drug information provided by pharmacists is generally given at the early stages in determination of drug therapy, pharmacists should acquire the ability to provide more advanced clinical pharmacy practices based on the clinical pharmacokinetics and pharmacodynamics.

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Our hospital developed a dispensary inspection system for injections in October, 2001 as a preventive measure against the administration of wrong instillations due to a misidentification of patients and started a service for delivering the injections prepared at the pharmacy to the patients' bedside. The injections delivered by pharmacists are those for instillation prepared at the pharmacy to be administered between 10 : 00 and 22 : 00. The injection delivery service was monitored by the dispensary inspection system using two-dimensional codes (QR codes) printed on the labels of instillation bottles at 3 points, i.e. at dispensing, at delivery, and at administration. The number of cases in which pharmacists were warned by the injection dispensary inspection system and the circumstances of warning were investigated during the 4 months from February 1 to May 31, 2002. During the 4 months, 3 (0.04%) of the 7, 690 deliveries of injections by pharmacists to the patients' bedside were misidentified. All misidentifications were caused by human error. The close involvement of pharmacists in the delivery of injections has contributed to the prevention of accidents due to the erroneous delivery of injections.

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It is important for patients to receive the pharmaceutical care established by a common understanding between community and hospital pharmacists through the whole medical treatment terms including out and in hospital. We therefore developed to the following training materials consisting of 8 components, 1. Case study charts, 2. Items on pharmaceutical management, 3. Items on pharmaceutical services, 4. Sheets for recording the medical history, 5. Sheets on drug information of patients, 6. Sheets on the contents of pharmaceutical services, 7. Confirmation sheets for essential drugs and 8. Check sheets for essential drugs on 6 diseases, such as left deep-vein thrombosis, myocardial infarction, hypertension, non-insulin-dependent diabetes, bronchial asthma and gastric ulcer. In the present study, which is a continuation of a previous paper, to evaluate the usefulness of these training materials, a questionnaire regarding the benefits, of “points 2, 3, 7 and 8 mentioned above” on community and hospital pharmacists selected randomly was conducted and analyzed. Both community and hospital pharmacists evaluated the training materials to be highly advantageous. Furthermore, pharmaceutical services of pharmacists to the patients were also improved by introduction of these methods. These findings reveal that it is useful to use training materials to help improve the skills of pharmacists.

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Beginning in 1986, a large number of cattle were found to be infected with BSE in England, eventually reaching approximately 180, 000 cattle in 2001. On March 20, 1996, the Consultative Institution of the Agriculture Ministry in England issued a statement that Variant Creutzfeldt-Jakob Disease is closely related to BSE. In Japan, an outbreak of BSE was confirmed in 2001.
BSE has become a big social problem in Japan. Urgent Warnings and announcements appear on the front page of the web site of the Ministry of Health, Labour and Welfare. Regarding pharmaceutical materials that originate in cattle, the Ministry of Health, Labour and Welfare has instructed as follows : The use of materials from England is prohibited (1996); The country of origin and the internal organs used in cattle-derived products must be specified, and materials from high risk countries must be substituted with others (December 12, 2000); The use of products from countries with unknown risks must be discontinued, and all prohibited materials that have been repackaged for market must be recalled (October 2, 2001). The Ministry subsequently announced additional measures : Recall information related to BSE would be carried on a new pharmaceutical information providing system. This program continued until January 10, 2002.
At Uwajima City Hospital, we decided in December 2000, to stop using cattle products, and in October 2001, we asked pharmaceutical companies to report their measures regarding the country of origin and cattle body parts of their products.
According to the recall information carried on the web site (http://www.pharmasys.gr.jp/) of The Organization for Pharmaceutical Safety and Research, and the answers received from the pharmaceutical companies, we investigated what measures had been taken. Any prohibited medical materials which were still being supplied in December 2000 were requested to be recalled according to the risk classification. We found that we did not have enough information from the pharmaceutical companies. In particular, when we did not actively inquire, the information reported was insufficient. Although the recall of products related to BSE is preventive, it is important that reliable information be provided to medical institutions in order to use unrecalled products without worry. We ought not to depend on passive information, and should always deal with such a crisis actively under the guidance of the authorities, as reported on the web site of the Ministry of Health, Labour and Welfare.

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To evaluate the optimal dosage for fluconazole based on the pharmacokinetics, we monitored the serum fluconazole concentrations in seventy-seven inpatients who received a fixed maintenance dose of fluconazole for at least 7 days. A significant negative and a positive correlation were obtained between the C/D ratio (trough concentration/dose/body weight) and the creatinine clearance (Ccr; r²=0.287), and the C/D and the urea nitrogen (BUN; r²=0.234), respectively. No significant correlation was obtained between the C/D and age (r²=0.0232). There was no difference in the C/D between patients receiving medication intravenously and orally (p=0.635). The relationships between the dosage and serum trough concentration were as follows : Ccr≥50 group : y=3.54x-1.07 (r²=0.877), Ccr<50 group : y =3.59x+8.20 (r²=0.504). About 50% decrease in serum fluconazole concentration was observed in patients received hemodialysis (HD) therapy. No significant difference was observed in the C/D between patients received CHDF therapy and patients whose Ccr above 50 mL/min (p=0.263). These results suggest the following conclusions :
1 The optimal dosage of fluconazole is 5-10mg/kg/day in patients whose Ccr are above 50mL/min.
2 TDM is needed in patients with decreased renal function.
3 A higher dosage of fluconazole is needed to maintain the therapeutic level in patients undergoing HD or CHDF.

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The cause of coring was researched using a combination of 6 types of injection needles and 5 types of rubber stoppers. The research was carried out by sticking a needle into a rubber stopper 30 times, and observing the core in the vial and also observing the interior of the stopper. As a result, the rubber stopper with the least amount of coring was the newly developed S 2-210N1. However, depending upon the needle used, coring occurred and protrusions and cracks in the rubber were confirmed in the interior of the rubber stopper. The best injection needle was found to be the PenNeedle 31G (PN 31 G needle). However, coring occurred when used with the rubber stoppers PenFill R 300U and HumaCart R300, which are currently sold on the market. The least amount of coring occurred with the combination of the S 2-210N1 and the PN31G. In addition, while an extreme amount of coring occurred with a MicroFine Plus 31G (BD31G needle) cut needle tip, little coring occurred with the non-cut needle tip, and it was discovered that the make-up of the needle tip of the injector is closely related to such coring. The cause of the core occurrence was thus found to be the make-up of the needle tip and the material of the rubber stopper. In addition the affinity of both parties is also related. Therefore, in order to prevent coring it is advisable to change the rubber stoppers of insulin medicine to a rubber that does not cause coring, and to use an injection needle with a make-up close to the PN31G needle. In addition, the rubber stopper and needle combination for such usage needs to be further evaluated.

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We investigated a highly sensitive method to determine the degree of fibrosis of various organs by Liquid chromatography/ Mass Spectrometry (LC/MS). The results suggested that the method of LC/MS for determining hydroxyproline had a significantly higher sensitivity than colorimetric and fluorescent labelling methods. In addition, the effect of complex amino acid components from living body samples mixing with hydroxyproline was eliminated. According to the peak observed on the chromatography findings, the molecular structure of hydroxyproline could be accurately identified. Therefore, we concluded that the new method of LC/MS was very useful for measuring hydroxyproline in living body samples containing large amounts of complex amino acid components.

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Yokohama City University Medical Center was renovated in January 2000 and a total ordering system was established. To improve the dispensing work for injections, an automatic ampoule dispensing system, which picks up injections automatically according to an individual prescription, was introduced. We investigated the effectiveness of the automatic ampoule dispensing system regarding the progress of pharmaceutical services in medical wards.
We improved the automatic ampoule dispensing system twice after its initial deployment. The number of prescriptions for injections, inpatients, the time required for prescription printing, the time required for dispensing, the number of dispensing errors found and inquiries regarding the prescriptions were counted for 12 months.
After the first improvement, the dispensing time required was shortened by 25% by changing the manner of transmission of the prescription data. The printing time was shortened by 45% by employing a high-speed printer. The number of inquiries regarding prescriptions increased by eightfold with the saving of the time required for the dispensing itself.
The introduction of the automatic ampoule dispensing system was thus found to be useful in order to save time related to dispensing work and thereby improving the quality of pharmaceutical services for inpatients.

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We report 2 patients who received medical guidance during immunosuppressive therapy involving the administration of antithymocyte globulin (ATG) and cyclosporin A (CyA) for complicated aplastic anemia. In case 1, during the second administration of ATG, side effects manifested as allergic reaction and serum sickness. In case 2, the side effects after the first administration of ATG were the same as those in case 1. An antimycotic drug that can increase the blood concentration of CyA was also administered in case 1. The BUN level, which is a marker of renal function, was slightly elevated. In both cases, drug compliance for CyA was good, and the trough blood concentration of CyA remained within the objective concentration. Levels of leucocyte, neurophils and thrombocytes tended to the recover after combined administration of both drugs in the 2 patients. However, the patient's quality of life (QOL) decreased remarkably due to a deterioration of the stomatitis, since the host was immunocompromised. The patient's QOL improved by the administration of narcotic analgesics. In case 2, the stomatitis did not worsen, since infection was prevented by the use of a clean room and care of the oral cavity. This study suggests that appropriate pharmaceutical care during immunosuppressive therapy contributes to QOL maintenance in patients with aplastic anemia.

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In recent years, Methicillin-resistant Staphylococcus aureus (MRSA) is considered to be major causative bacteria of severe hospital infections resistant to antimicrobial agents, and the measures against increasing MRSA infections is a great concern in the Japan medical field.
Our hospital established an Infection Control Team (ICT) for hospital infection control in December 1998.
ICT searched and analyzed a comparative study regarding the use of injectable anti-MRSA agents such as vancomycin, arbekacin, or teicoplanin, while the latter half 1998 (July 1998 through December 1998) and the latter half 2001 (July 2001 through December 2001). As the result, the quantity of injectable anti-MRSA agents showed a decrease from 1998 to 2001.
Next, a questionnaire was conducted among doctors in our hospital to obtain a consensus for the proper use of anti-MRSA agents in October 2001. The questionnaire was sent to 220 doctors and recovered from 179 doctors (recovery; 81.4%). The following strategies were consented to by more than 90% of all responses; “Keep hospital policies dealing with control of hospital infection”.
Our data suggests that the ICT activity is an effective program for controlling hospital infection and we need to further enhance the awareness of hospital infection control among all doctors in our hospital.

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The effect of timing on the administration of spherical charcoal (Kremezin) on the pharmacokinetics of valproic acid (VPA) in the coadministration of sodium valproate and Kremezin was examined in rats.
Kremezin, when administered either immediately or 30 min after the administration of sodium valproate, significantly decreased the area under the plasma concentration-time curve (AUC) _0-3 of VPA by about 30%. In addition, when Kremezin was administered 30 min or 1 hr before sodium valproate dosing it decreased the maximum plasma concentration (C_max) of VPA by 39% and 27%, respectively, and significantly decreased the AUC_0-3 of VPA by 54% and 45%, respectively. The plasma VPA concentrations in all Kremezin-treated groups were significantly lower than those in the controls. However, Kremezin administered 1 hr after sodium valproate dosing had no effect on the plasma VPA concentration, C_max or AUC_0-3 of VPA.
These results suggest that Kremezin decreased the absorption of VPA due to adsorption after the coadministration of sodium valproate and Kremezin.

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In our hospital, the dosage form of phenytoin (DPH) was switched from hospital pharmacy-made 50% fine granules to commercial 10% powder. We surveyed the change in the serum DPH concentration in epileptic patients administered both DPH formulations, and examined the pharmaceutical differences associated with the disposition of DPH. About a 25% elevation in the steady-state serum DPH concentration was found after changing from 50% fine gfanules to 10% powder, thus indicating the increase in the amount of DPH absorbed from the gastrointestinal tract. In a dissolution test, the rate of DPH release of 10% powder was similar to that of 50% fine granules irrespective of the medium conditions. These results were strongly suggestive of a bioequivalence between 50% fine granule and 10% powder in clinical practice. In dispensing 50% fine granules, there was not only a significant weight reduction at the dividing and packing steps but also considerable adsorption by the package, although this phenomenon tended to be attenuated by mixing the drug with lactose as vehicle. On the other hand, the 10% powder was highly recovered probably owing to the enhanced fluidity. There was no change in the DPH content per weight before and after dispensing process in each formulation, thus showing that the degree of weight reduction was consistent with that of the DPH loss. Based on the relative weight recovery of the preparations during the dispensing process, it is presumed that the ingestible dose of DPH was increased by about 6% due to the formulation change. The significant increase in serum DPH concentration after formulation change is likely to be attributed to an improvement in the dispensation loss prior to administration, because DPH shows non-linear pharmacokinetics within the therapeutic range. We consider that monitoring the serum DPH concentration is required especially when the other dosage forms are prescribed.

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The major elimination route for histamine H₂-receptor antagonists (H₂-antagonists), such as famotidine, ranitidine, and cimetidine, is urinary excretion. Therefore, if the dosage adjustments for renally impaired patients or elderly patients are improper, such patients will likely have adverse effects such as mental confusion andseizures due to these drugs. In the package inserts of these H₂-antagonists, methods for adjusting the dosage according to the creatinine clearance (CLcr) are provided. In this study we investigated the prescription profiles of famotidine, ranitidine, and cimetidine for inpatients during a three month period at the Kansai Rosai Hospital. The CLcr values were estimated based on the serum creatinine concentration, age, and body weight of each patient according to the equation of Cockcroft and Gault, in order to consider the appropriate usage of H₂-antagonists from the relationship between the patient's renal function and dosage. More than 70% of all patients who were prescribed the H₂-antagonists were elderly patients (more than 60years old), and 37% were found to have their estimated CLcr to be less than 60mL/min. The dosage for 22% of patients was calculated to be excessive according to the estimated CLcr. These results indicated that prescription monitoring by hospital pharmacists according to the patient's CLcr may contribute to the appropriate dosage management of H₂-antagonists for inpatients.

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In hospital risk management, it is very important for pharmacists to prevent not only cases with risk in which the pharmacist is concerned directly, but also drug-related accidents. In particular, pharmacists must sufficiently recognize the intention of a physician's hypnotics to prevent drug-induced tumbling accidents. However, at Ehime University Hospital, hypnotics are not controlled by the patient directly, but by nurses are distributing it at the diagnosis and treatment department when necessary. It is necessary to grasp the degree of recognition for the hypnotics of the nurse in order to reduce a risk of tumbling accidents by patients using such hypnotics. In the present investigation, a questionnaire on hypnotics usage was carried out for nurses of Ehime University Hospital. As a result, nurses considered that hypnotics were related to the tumbling accident but hypnotics were necessary for the patient complaining of insomnia. In spite of knowing the drug's name and the characteristics on benzodiazepines well, it was clear that nurses did not know about the muscle relaxant action of benzodiazepines and the fact that new medicine has a weak muscle relaxant action. It is necessary for pharmaciststo provide sufficient information on the hypnotics in order to understand the meaning of the hypnotics prescription of doctors sufficiently. In addition, information must be given to nurses regarding the efficacy and side effects of hypnotics which then should be provided to patients being medicated by hypnotics.

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To analyze the students' levels of knowledge of technical terms in taking medicines and to utilize the results for drug education in the future, we gave a questionnaire to students of junior-high (n=322), nursing (n=84), paramedical (n=197) and medical (n=151) schools in Yonago City, Japan, in 2002. The students were requested to fill out on the unsigned self-entry type questionnaire asking the meanings of 20 technical terms and 4 words about social common sense.
The number of correct answers for “generics” and “over the counter (OTC) drugs” was small in all subjects. Often reported in the mass media, both terms are within the category of social common sense. Students who are future specialists in medical care should pay more attention to both terms, which seemed to be taught evenin college lectures. The ratio of correct answers (mean±SD) in junior-high students was as low as 3.2±2.4/20. Even medical students, who are expected to exercise leadership in health guidance, only had comprehended half of the 20terms : general students of similar ages would correctly answer much fewer items.
Teachers should interpret medical terms to students more closely than to adults when they lecture on the use of medicine administration at hospitals and pharmacies, and must confirm whether the students understand the terms correctly. Furthermore, to give “more education on pharmacy and health” seems to be necessary for children at an early age. We propose that for compulsory education in Japan, an infrastructure system should be established in which pharmacists, who are specialized in drugs, participate actively in school lectures.

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In the initial treatment period until laboratory data is available, physicians empirically administer antimicrobial agents to infected patients. Consequently, doctors require scientific evidence for the use of antibacterial agents during this initial empirical period. We have produced Guidelines for the Use of Antimicrobial Agents to meet this medical need
Initially, we classified the antibacterial preparations into eight groups according to the organs infected. Subsequently, in each infected organ, we calculated the bacteria numbers and grades of sensitivity for each antimicrobial agent. Finally, we calculated the probability of successful treatment outcomes for each of the infected organs.

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Chronic hemodialysis outpatients take various medicines for a long time, and require 3 or 4 hours for one hemodialysis treatment. Therefore, we should give peninent information efficiency in order to maintain their quality of life. The purpose of this study was to investigate the knowledge of medication statistically on chronic hemodialysis outpatients from the pharmacist's point of view and to inspect the capable instruction in medication.
The 63 chronic hemodialysis outpatients, who had received instructions in medication at Towa hospital during February and March 2002, were selected by random sampling. For them, we carried out the questionnaire by interview and inquiry into medical reports. We converted the answers to the score on knowledge, and made a correlation analysis between the score and the patient's background. In addition, we made a simple regression analysis, using the one way analysis of variance (ANOVA), and the Tukey-Kramertest.
We obtained the following results : 1. The score on knowledge of medication was 11.2±4.6 marks out of 25.2. Regarding the score on knowledge of medication, the group in the age younger than 60 moreover in the duration of hemodialisis above 5 years (15.7±2.5 marks) and the group in non-diabetes mellitus (12.3±4.4 marks) wee significantly higher than in the other groups. 3.25.4% of all patients understood about side effects, 14.3% worried about interactions with some medicines, and 58.7% had made mistakes in medication One or more times.
In the light of these results, we propose that we can infer the knowledge of medication from the background of patient, such as age, the duration of hemodialysis, disease, and we can prepare materials based on the ability to understand their medication for each patient. It is also beneficial for increasing efficiency to standardize method and points of instruction, because we will be able to use more exact information even for new patient and thus make a plan of the instruction in a timely manner for such patients.

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In a clinical medication, two or more medicines are often prescribed for a patient. For the effective and safe use of medical supplies, it is thought that various checks should be performed at the time of a prescription order entry and an injection order entry. However, the widely used order entry check system for a prescription order and each injection order is carried out in many cases independently. From a viewpoint of the proper use of medical supplies, the check system for a prohibited combined use is required regarding prescription-injection. We extracted the prescription and injection data of all patients, and checked for drug interactions. Although there were few cases of actual contraindicated combined use of the prescription-injection based on a check of the data, since there were very many the combination variations, it was suggested that it is necessity to check the combined use of prescription-injections. In the present condition from various factors, since changing the order entry system is impossible, as an alternative, in case an individual set of inpatient's injections is performed, patient's data should be checked by our system, and an interaction check of prescription-injectioshould be done, while also informing the doctors in charge of all findings. By continuing such examinations and informing the results to all doctors at our hospital, the proper use of medical supplies should thus be improved.

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In drug information management, it is necessary to obtain and evaluate the latest information. Patient information is also useful for providing safe and effective pharmacotherapy. We studied the state of providing of information sources enabling pharmacies to practice superior drug treatment, including drug evaluations, to enhance the quality of medical care.
A survey on drug information sources, including books and academic journals, and medication notebooks was conducted while targeting the members of the Chiba Pharmaceutical Association. From the aggregate of pharmacies in the 23 chapters of the Chiba Pharmaceutical Association (a total of 1, 833 pharmacies), 30% were randomly sampled in a questionnaire survey on drug information sources and medication notebooks. The response rate was 46.6%.
A total of 97.7% of the responding pharmacies possessed books. However, the percentage of pharmacies with regular subscriptions to one or more academic journals was only 54.5%. In addition, internet use was only 46.3%.
Medication notebooks were distributed at 95.3% of the pharmacies, particularly to the very young and elderly patients. Notebooks were found to be useful for avoiding duplicate dosing (72.0%) as well as for treating patients with concomitant drugs (71.6%).
Pharmacies are well stocked with tertiary sources such as books but are still inadequately supplied with primary sources such as journals. Many pharmacies make use of medication notebooks, thus suggesting that information on drug safety is especially useful. In the future, pharmacies will need to take steps to secure more primary information and better evaluate all drug information to improve the quality of drug information management.

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We manage most of medical slips by writing down information by hand, because our hospital does not have an ordering system. For instructions on cancer chemotherapy, we suggested that posting instructions of the medical card in the injection prescription by each medicine bottle could lead to the possibility of some medication errors on account of 1) a risk for posting errors and 2) difficulty of general inspection. To improve the present situation, we established a system called “Prescription-Instruction Sheet of Chemotherapy” and have utilized it since July, 2001. It is made up of triple carbon paper A 4 size which is printed on the whole protocol of chemotherapy. It shows three functions, namely a prescription, a copy of the ward and an instruction sheet for nurses, as soon as a doctor fills in the blanks on the sheet.
One year after introducing this system, we investigated a questionnaire to ask about the usefulness of this sheet to the medical stuff. The results were highly satisfactory, because most opinions mentioned that the posting of medical cards become unnecessary and the schedule is easy to understand at first sight. Nurses had some recommendations to improve this sheet. On the other hand, the number of incidents and accident reports decreased after introducing this system to the department of nursing.
We conclude that this system helped to improve the risk management owing to the establishment of this new system.

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