Currently,much importance is being placed on developing policies to ensure that medical costs are adequately monitored in Japan.Therefore,medical institutions must achieve a balance between maintaining and improving the quality of medical services and efficiently managing them.
Though pharmacists are helping to improve the quality of medical care through the promotion of proper drug use,whether this actually contributes to the management of medical services has not been investigated.Up till now,doctors have prescribed medications at their own discretion based solely on their assessment of the patient’s condition but if there could be discussion on the most appropriate medications for patients with other medical professionals,particularly pharmacists,this would increase opportunities for drug use.
We have previously reported the results of our analyses of the contribution of pharmacoeconomics to hospital management,evaluation of choice of medication,and team medical treatment,and in this review,present some specific examples.Our findings indicate that pharmacists can contribute to raising the quality of drug therapy and medical management.Furthermore,they should also help to expand the role played by pharmacists in medical institutions.

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We performed operations research with the aim of devising measures to promote cooperative instructive operations at discharge from hospital.Our source data were individual data from a survey of the current status of instructive operations at discharge from hospital targeting the 998 member institutions of the Japanese Society of Hospital Pharmacists.
We performed one-way analysis of variance in which explanatory variables were set as attributes of institutions and determined factors associated with the presence or absence of cooperative instructive operations at discharge from hospital by performing multiple logistic regression analysis for the related items.We then grouped the institutions according to the institutional attributes and performed a correspondence analysis (III class in quantification) based on the cross-table results between the groups and the reasons why some institutions do not perform cooperative instructive operations at discharge from hospital.In our role as members of the Recuperation Sickbed Committee,we then drew up an action plan based on the survey results.
Both presence or absence of cooperative instructive operations at discharge from hospital and institutional attributes were significantly related to both the number of set operations (number in regional alliance section,etc.) and prescription types (in-hospital or out-hospital) within a hospital.Institutions which had more operation items and more out-of-hospital prescriptions tended to conduct cooperative instructive operations at discharge from hospital more (Odds ratio : 1.65 and 1.97).Such institutions are considered to be in a better position to perform cooperative instructive operations at discharge from a hospital.However,we felt that they would have more chances to conduct operations,if they remedied“inadequacies in their institutional systems”which was given as a reason for not conducting operations.

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Epadel S®,a seamless capsule form of ethyl icosapentate (EPA-E),was made into a suspension in 20 ml of hot water (55°C) and stirred with a polystyrene (PS) disposable spoon.When left in the suspension,the surface of the spoon started to dissolve after 45 minutes,and was completely dissolved after 12 hours.We also investigated the dissolution of PS utensils in suspensions made from teprenone (Selbex®) capsules or powder,or gefarnate (Gefanil®) capsules.
Up till now,there have been no reports of toxicity due to PS or the non-reactants and/or by-products produced in the PS production process.However,as the dissolution of spoons,cups or other common utensils made of PS in drug suspensions could cause concern among patients,caregivers,and medical staff,it is important to instruct them to avoid the use of such utensils when preparing drug suspensions.

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In November 2007,in order to prevent the emergence of drug-resistant bacteria,we established a notification system concerning usage of broad-spectrum antimicrobials (carbapenems,fourth-generation cephalosporins,quinolones,and antimethicillin resistant Staphylococcus aureus (MRSA) agents),and linked it to a hospital information system.When ordering any of the antimicrobials mentioned above,physicians need to input the reason for prescribing it as well as the status of submitted bacterial cultures,and the period of administration is restricted to a maximum of four days including the day of order entry.
In order to evaluate the system,we compared the amounts of regulated antimicrobial agents prescribed each month,the number of patients they were administered to,culture submission rate,the susceptibility rate of Pseudomonas aeruginosa for carbapenems and number of Clostridium difficile toxin A samples,between 1 year before the introduction of the system and 1 year after it was introduced.While there was no decrease in the amount of the regulated antimicrobials prescribed overall,there was a significant decrease in the amount of fourth-generation cephalosporins prescribed (p<0.05).The total cost of the antimicrobials did not decrease because the amounts of unregulated antimicrobials increased significantly (p=0.0002).The proportion of patients using regulated antimicrobials decreased significantly,from 17.3% to 13.8% (p<0.0001),and the frequency of ordering blood cultures increased from 26.1% to 53.8% (p<0.0001).In addition,the susceptibility rates of Pseudomonas aeruginosa for meropenem and imipenem/cilastatin significantly improved (p=0.0325,p=0.0188),and the number of Clostridium difficile toxin A samples decreased (p=0.0365).
In conclusion,a hospital information system-linked prior notification system concerning broad-spectrum antimicrobials can make a useful contribution to preventing the emergence of bacterial resistance.

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The purposes of this study were to demonstrate how the interaction between rifampicin and voriconazole can be managed clinically and to characterize the changes in voriconazole concentration levels after discontinuation of rifampicin.The concomitant administration of voriconazole and rifampicin is contraindicated because the interaction between these drugs results in a subtherapeutic concentration of voriconazole.In this regard,voriconazole is known to be metabolized by CYP2C19,2C9,3A4,and rifampicin is a potent inducer of CYP3A4.
The interaction between rifampicin and voriconazole was investigated in a 70 year old male patient with severe infection in a prosthetic graft,necessitating simultaneous treatment with vancomycin and rifampicin.Rifampicin therapy was discontinued to start antifungal treatment with voriconazole.Interaction between the 2 drugs was evaluated by measuring voriconazole trough levels 4,7,11,18,and 29 days after starting therapy with it,performing the assays by high-performance liquid chromatography.
Four days after starting voriconazole,we observed a significant decrease in its serum concentration,to 0.24μg/mL.After 7 days,it had increased to 0.84μg/mL and to 1.24μg/mL after 11 days,and thereafter,continued to gradually increase.Thus,after discontinuing rifampicin,CYP induction continued to be strong for the first 11 days and then became more moderate over the course of a month.
In conclusion,it is essential that patients being treated with both rifampicin and voriconazole have their voriconazole concentrations monitored when rifampicin therapy is discontinued.

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There is an increasing need for the participation of pharmacists in cancer chemotherapy in order to ensure the proper use of drugs.Therefore,a postgraduate education program on cancer chemotherapy to enhance the knowledge and skill of pharmacists and give them a professional attitude could contribute much to it.
The postgraduate education program in cancer chemotherapy (master course,25 students) at Mukogawa Women’s University has 3 major parts.In the first,students gain a basic knowledge of the toxicity of anticancer agents in anticancer injection preparations,in the second they receive training in the withdrawal technique using a pre-filled vial containing simulated fluorescein sodium (FL) and in the 3rd,the extent that the 25 participants are exposed to the simulated anticancer drug (FL) when the PhaSeal® protective system is used and in its absence is measured to demonstrate the importance of the using PhaSeal® or some other protective system.
The extent of exposure was evaluated from the number of splashed-FL spots.When using PhaSeal® ,the number of spots was much less than without it.Also,the score for the level of skill as measured using a checklist was much greater when the PhaSeal® system was used than when it was not used.However,in a questionnaire on items such as the preparation of anticancer agents and the usefulness of the PhaSeal® system,though almost all of the students recognized its importance,some thought that its introduction in a hospital or community pharmacy might not be possible due to its high cost.

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We evaluated the effectiveness of preventing cholinergic crisis due to Ubretid tablets using a notice in electronic medical records concerning the initial dosage and the correct timing for increasing the dose.We also conducted a survey to investigate doctors’knowledge of the Ubretid tablet and opinions of the method used for displaying the notice in electronic medical records.
Displaying the notice resulted in a 4-fold increase in prescriptions with the proper initial dosage though there was no change in prescriptions giving the correct timing for increasing the dosage.Overall,there was a nine-fold increase in proper prescriptions giving the correct initial dosage and correct timing for increasing the dose.The survey of doctors revealed that they had little knowledge of Ubretid tablets and therefore considered the use of a notice in electronic medical records to be a very useful.
These results suggested that displaying such a notice in electronic medical records could be a useful and an easy way of preventing cholinergic crisis due to Ubretid tablets.

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Though antineoplastic agents are widely used in the treatment of cancer,genotoxic carcinogenic antineoplastic agents have mutagenicity and carcinogenicity risks for healthcare workers.Also,as it has been reported that higher concentrations of the antineoplastic agent Cyclophosphamide (CPA) were detected in the urine of healthcare workers involved in the preparation and administration of CPA,it has been speculated that they may inhale considerable amounts of CPA.However,no tests on the vaporization of CPA have been conducted.
This study aimed to clarify the amounts of CPA vaporized from physiological saline solution at different temperatures.The drug solutions were prepared as they would be for treating patients and placed in glass containers,maintaining the solutions at 20°C,25°C,30°C and 40°C for 3 hours,respectively,using a temperature controlled water bath.The vaporized CPA was absorbed by the silica gel in an air-sampler,extracted using methanol and quantified by LC/MS.At 30°C and 40 °C,amounts of vaporized CPA detected were 0.52 ng and 0.93 ng,respectively but were below the detection limit (0.16 ng/ 36 L) at 20°C and 25°C.Despite these results,however,in consideration of the formation of aerosols during the preparation of CPA solutions,appropriate precautions should still be taken to reduce the risk of exposure to CPA for healthcare workers,as described in the guidelines for preparing injection and antineoplastic agents aseptically.

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Oxaliplatin (L-OHP) in combination with infusional 5-fluorouracil/leucovorin (FOLFOX) has been established as a core therapy for advanced and recurrent colorectal cancer.In this case,sensory neurotoxicity is its dose-limiting toxicity.We evaluated it using the Neurotoxicity Criteria of DEBIOPHARM and conducted a retrospective analysis to determine sensory neurotoxicity-associated clinical factors.
Seventy patients with advanced recurrent colorectal cancer who received FOLFOX 4 therapy from November 2005 to February 2008 were the subjects of the present study.The median number of courses until expression of grade 1 neurotoxicity was six (range 1~17 courses) and that for grade 2 neurotoxicity was ten (range 3~18 courses).
A logistic regression analysis performed to determine patient background and laboratory data that affect the incidence of sensory neurotoxicity revealed that risk factors involving sensory neurotoxicity were WBC(×~10³/μL)[odds ration: 0.7556 (95% confidence interval:0.6740-0.8471)],Amylase (Logarithm natural)[1.7766:(1.0879-2.9011)],Transition [1.7850:(1.1647-2.7354)]and L-OHP cumulative dose (g)[2.2399:(1.5810-3.1734)].
These findings suggest that pharmacists should carefully monitor the rational symptoms in patients undergoing FOLFOX for advanced and recurrent colorectal cancer,particularly in those with risk factors for sensory neurotoxicity.

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The outcomes of cancer chemotherapy have been improved remarkably by the development of new anti-cancer drugs and regimens.However,the adverse reactions in cancer chemotherapy are more severe than those in other pharmacotherapy.In order to perform more effective and safer cancer chemotherapy,we developed a novel prescription checking system for drug-off periods in the administration of oral anticancer drugs.The new system consists of prescription history,duration of drug exposure,and comments columns and makes prescription checking easier and more efficient than with the former complicated system.Furthermore,following its introduction,the number of pharmacist interventions on prescriptions increased 7-fold.
The results of the present study suggest that our new prescription checking system contributes to raising the safety and effectiveness of drug therapy in outpatients taking oral anticancer drugs.

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The simple suspension method is a recently developed technique for the administration of tablets or capsules by tube.The drugs in their original dosage forms are directly suspended in hot water (55°C) so that they can be delivered through a tube.In the present study,we evaluated the recovery of drugs regarded as unsuitable for the simple suspension method.
After fine granules of Gramalil® and its generic equivalents had been put in syringes to make suspensions in hot water,tiapride hydrochloride was mainly detected in the suspensions forced out of the syringes,suggesting that it would be possible to conduct tube administration by this method.However,when the suspensions were prepared in cups,the amount of tiapride hydrochloride to be administered was found to vary,indicating that this method was unsuitable for conducting the tube administration of Gramalil® and its generic equivalents.
On the other hand,making suspensions of the contents of Pontal® capsules by either of the above 2 methods was found to be unsuitable for tube administration because the recovery of mefenamic acid was consistently low,though the findings for making suspensions of Pontal® tablets in a syringe suggested that tube administration by this method would be feasible.
The results of the present study indicated that if residues are observed on administering these drugs by tube using the simple suspension method,the amount of drug actually administered to a patient depended largely on its water solubility and the types of additives used.

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