Mycophenolate mofetil,an important immunosuppressant drug,is widely used for the prevention of rejection in organ transplants.Although there have been several studies on the effectiveness of therapeutic drug monitoring (TDM) for kidney and heart transplants,there have been few on TDM for MMF in liver transplants.In the present study,blood concentrations of mycophenolic acid (MPA),an active metabolite of MMF,were measured in 56 liver transplant patients treated with the drug at Kumamoto University Hospital since June,2004.Furthermore,a correlation between trough levels and the efficacy and/or adverse effects of MPA was investigated.MPA trough levels tended to be high in patients exhibiting clinical efficacy but intra- and inter-individual variations in trough levels appeared to be very large.The average MPA trough levels for each patient ranged from 0.2-5.8μg/mL.The coefficient of variation in trough levels among individuals was found to be 19-144%.We also investigated a relationship between cytomegalovirus (CMV) infection,a secondary adverse effect of MMF,and MPA trough levels.The anti-virus drug,ganciclovir (GCV) had been given to 19 patients but we found no significant relationship between trough levels and whether patients had been treated with this drug or not.
As the present study did not properly clarify the clinical implications of MPA trough level measurements,detailed investigation of the pharmacokinetics of MMF/MPA in liver transplants and the determinants for intra-/inter-individual variations will be necessary.

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The authors retrospectively reviewed the incidence and severity of adverse events in 45 in-patients with Non-Hodgkin’s Lymphoma who had received chemotherapy consisting of rituximab (375mg/m²)and either CHOP[cyclophosphamide: CPA (750mg/m²),adriamycin:ADR (50mg/m²),vincristine : VCR (1.4mg/m²),prednisolone : PSL (100mg/body/day)]or THP-COP[CPA (650mg/m²),pirarubicin (tetrahydropyranyl adriamycin):THP (40mg/m²),VCR (1.0mg/m²),PSL (40mg /m²/day)]at Iwate Prefectural Central Hospital.We also analyzed the risk factors of febrile neutropenia (FN) in patients receiving both chemotherapies.
Age and PS were significantly higher in the THP-COP group,and body surface area and a dosage were significantly higher in CHOP group.Regarding hematotoxicity,adverse events defined as grade 3 or 4 in the Common Terminology Criteria for Adverse Events version 3.0 (CTCAE v.3.0) were observed with high frequency in both groups.In the THP-COP group,the frequency of anemia of more than grade 3 was significantly higher (52.2%,p<0.05)and the period required to recover from nadir was significantly longer (13.8±7.3 day,p<0.05)
The frequencies of the subjective symptoms of constipation and peripheral neuropathy were high in both groups,and that of alopecia of grade 1 was significantly higher (50.0%,p<0.05)in the CHOP group.
Low serum albumin levels (odds:0.088,p<0.05)and a fasting blood sugar level of more than 126mg/dL (odds: 12.003,p<0.05)were risk factors for FN in both groups.
These results suggest that with regard to FN and other adverse events that may occur during CHOP and THP-COP chemotherapies,great caution should be exercised with respect to blood counts,serum albumin levels and blood glucose levels.

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Low dose aspirin acts as an antiplatelet agent through irreversible acetylation of platelet cyclooxygenase (COX)-1,which inhibits platelet aggregation.Nonsteroidal anti-inflammatory drugs (NSAIDs) have a similar mechanism of action to aspirin,and may interact pharmacodynamically with it.In view of this,we performed an in vitro experimental study in which 6 NSAIDs with various COX-1 activities were added to human blank blood to investigate the influence of each one on the antiplatelet action of aspirin.
Platelet rich plasma (PRP) was obtained from 8 healthy volunteers (23.3±3.2 years old).After adding aspirin (plasma concn.: 16μg/mL) and NSAIDs (plasma concn.: maximal concentration in clinical use) to the PRP,aggregation was measured using collagen as the stimulus.We used the platelet-aggregation threshold index (PATI) as the index of aggregation activity for this study.
The PATI of a group in which aspirin was added after ibuprofen (Ibu→Asp) and that of a group in which both drugs were added at the same time (Asp+Ibu) were 3.54±0.80 and 3.53±1.01μg/mL,respectively.These were lower than the PATI for aspirin alone (5.17±1.18μg/mL),indicating interference with the antiplatelet effect by the NSAID.For the other 5 NSAIDs,the PATI obtained was similar to that for aspirin,regardless of the order of addition.The logarithmic value of the unbound drug concentration of each NSAID (D_f) divided by platelet COX-1 IC₅₀[log (D_f/COX-1 IC₅₀)]was correlated with its PATI (R=0.817,p<0.001),suggesting that the interaction between low dose aspirin and NSAIDs may be inferred from the level of inhibition of platelet COX-1 at clinical drug concentrations.

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While it is necessary to use antifungal drugs for opportunistic deep mycosis in patients with immune system dysfunction,the inappropriate use of such drugs needs to be reduced to prevent occurrence of antifungal drug resistance as well as from the pharmacoeconomic viewpoint.In this study,we evaluated a notification system for the proper use of antifungal drugs that was introduced at Ehime University Hospital in January 2008.We investigated changes in antimicrobial use densities (AUD) of antifungal drugs,dosage period,number of patients receiving them and average dosage period of antifungal drugs in β-D glucan negative or unidentified patients from January 2007 to December 2008.After the introduction of the notification system,there was a significant decrease in the average monthly AUD of antifungal drugs (from 12.8±1.8 to 7.6± 1.8 ; p<0.01).The number of patients treated with antifungal drugs for periods of over 12 days and the average dosage period of antifungal drugs in β-D glucan negative or unidentified patients also decreased (p<0.05).These results suggested that the notification system was effective in reducing purposeless empirical therapy and ensuring the proper use of antifungal drugs in our hospital.

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The availability of tablets and compliance are related to their size.Large tablets are easy to grasp,but are difficult to ingest.Therefore,tablets measuring 7 to 8 mm in diameter are commonly manufactured.It is difficult for elderly and disabled persons to grasp tablets of this size.Assuming that oral disintegrating (OD) tablets can be ingested even when they are large,we conducted an organoleptic test with model OD tablets in 84 persons aged over 65 years.Of these,76% reported that OD tablets measuring 15 mm in diameter were difficult to ingest.However,all subjects could ingest them.In addition,79% could ingest them easily.The results suggest that OD tablets measuring 15 mm or less in diameter are safe even in elderly patients in whom swallowing hypofunction is frequent.It was also shown that tablets measuring 13 mm in diameter were easier to grasp than those measuring 8 mm.If OD tablets are increasingly prescribed despite their size,it may reduce difficulty in grasping,and facilitate compliance in patients with mild dysphagia,as well as the simple suspension method (safe and useful tube administration method),improving patients’QOL.

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The over-the-counter (OTC) drug sales system has been deregulated in accordance with the revised Pharmaceutical Affairs Law since June,2009.With the revision,OTC drugs are now classified according to 3 levels of risk and a new qualification for the registration of drug sellers was established.In this study,we surveyed pharmacy students,pharmacists in hospitals and drugstores,and the general consuming public regarding their views on the revision of the OTC drug sales system in 2008 before it was revised.The views of students and pharmacists were almost the same except for those on the relief system for injury to health about which students had little idea.The survey also found that pharmacists placed emphasis on drug adverse effect information and cautions in use when they sold OTC drugs,while the consuming public focused on drug efficacy when they bought them.
The results of our survey suggested that views on OTC drugs differed depending on the standpoint of the person.Therefore,in order to play an important role in self-medication,pharmacists needed to acquire the communication skills necessary for providing the public not only with the information that they want but also the information that they need to have.

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Nausea and vomiting are major adverse reactions in cancer chemotherapy and affect patients’quality of life.Though medical institutions have revised their antiemetic therapy guidelines,there have been few evaluations of the revisions especially for the continuous administration of anticancer drugs.We revised our guidelines for antiemetic therapy in the continuous administration of anticancer drugs and then investigated the effect on the incidence of nausea and vomiting and cost of antiemesis.
Our subjects were 39 patients receiving high dose FP therapy (Day 1 : cisplatin 80mg/m² ; Day 1-5 : 5-fluorouracil 800 mg/m²)for esophageal cancer at Kobe City Medical Center General Hospital.A conventional antiemetic therapy group (conventional group) received granisetron 3mg on Day 1 (20 patients),and a revised antiemetic therapy group (revised group) received granisetron 3mg plus dexamethasone (DEX) 20mg on Day 1 and DEX 4-12mg on Day 2-5 (19 patients).The incidences of nausea and vomiting in the conventional group were 80.0% and 30.0%,respectively and in the revised group 52.6% and 15.8%,respectively.There were significant decreases in the incidences of nausea and vomiting in the revised group as compared with the conventional group on Day 2,3 and 5 and Day 3,respectively.The occurrence of vomiting was 0.80±1.88 times in the conventional group and 0.21±0.54 times in the revised group.
The cost of antiemesis for 1 course was 16,701±15,103 yen for the conventional group and 9,691±3,326 yen for the revised group.
These results suggested that our revised antiemetic therapy for the continuous administration of anticancer drugs could reduce the incidence of nausea and vomiting as well as the cost of antiemesis in cancer chemotherapy.

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TDM based on PK/PD (pharmacokinetics/pharmacodynamics) is performed to augment antibacterial effects and avoid adverse reactions.Recently,to enhance the effect of treatment,it has been recommended that target levels for PK/PD parameters are set high.However,in this case adverse reactions are a concern.
In this study,we investigated the efficacy and adverse reactions of vancomycin in patients infected with MRSA.No significant difference was found in AUC/MIC between an effective group and an ineffective group though AUC/MIC tended to be higher in the former.However,in an acute kidney injury group,AUC and trough levels of vancomycin were significantly higher than in a normal renal function group.There were patients whose vancomycin clearance decreased during administration,which suggested that the monitoring of clearance is necessary.Further,a change in the MIC for MRSA was noted in 50% of the patients during administration,which could influence the dosage calculated from AUC/MIC.

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Very little information is provided with OTC drugs and unlike prescription products,they do not have package inserts or interview forms.The purpose of this study was to examine the stability of 5 acetaminophen-containing OTC drugs by observing temporal changes in their characteristic physico-pharmaceutical parameters (hardness,mass,elution,drug migration) when they were preserved under conditions in which temperature and humidity were altered.From the results,it was assumed that 3 of the 5 drugs were affected by temperature and humidity,and that it was difficult to maintain stability when they were taken out of their packages.In particular,the drugs seemed to be more adversely affected the higher the temperature was and changes in parameters were greater.Also,the results of an elution test conducted after 24 hours of storage suggested that there was deterioration in 3 of the products.
In conclusion,our findings clearly showed that patients need adequate explanation on how to keep OTC drugs.

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At Gifu Pharmaceutical University,hospital visits were introduced as an early exposure program for first year students (n=144)in 2009.On conducting a questionnaire survey of students who had gone on a hospital visit (response rate 100%),the results suggested that pre-learning raised the students’interest in the hospital visit and that they were satisfied with it (2 -top ratios : 79.9% and 83.3%).We also conducted a factor analysis and covariance structure analysis to investigate a connection between“interest in hospital visit”and“level of satisfaction with hospital visit”and the learning structure.Three important factors were extracted in factor analysis of 14 questions relating to before the hospital visit:“presentation ability”,“understanding of hospital pharmacist duties”,and“basic knowledge of medicine”.Similarly,three important factors were extracted in factor analysis of 13 questions relating to after the hospital visit:“desire to be a hospital pharmacist",“active pharmacist”,and“positive attitude”.Covariance structure analysis showed that three factors:“presentation ability”,“understanding of hospital pharmacist duties”,and“basic knowledge of medicine” elicited“interest in hospital visit”.We inferred that this was linked with“hospital pharmacist desire”and“positive attitude”.We also inferred that 3 factors-“desire to be a hospital pharmacist”,“active pharmacist”,and“positive attitude”- raised the“level of satisfaction with hospital visit”.

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