We previously reported that the pharmacokinetics of metoprolol varied greatly among 34 Japanese patients in which the drug was routinely administered due to genetic polymorphisms of CYP2D6 (CYP2D6 *10 ),and that the racial differences in allele frequencies may be responsible for differences in metoprolol therapeutic dose ranges between Caucasians and Japanese.The aim of the present study was to evaluate mechanisms for pharmacokinetic variability of carvedilol and bisoprolol for personalization of β-blocker therapy in Japanese patients with heart failure (HF).The CL /F value of S-carvedilol was decreased in healthy Japanese subjects with CYP2D6 *10 ,although the effect of CYP2D6 *10 was not significant in HF patients.In addition,it was suggested that the activity for CYP2D6 and other carvedilol-metabolizing enzymes was decreased in HF patients.On the other hand,the CL /F value of bisoprolol was decreased in elderly patients.However,pharmacokinetic variability of bisoprolol was small even in routinely treated patients,provided that both body weight and renal function were taken into account for the prediction of CL /F of the drug.These results suggest that bisoprolol is a useful βblocker for the treatment of HF patients.

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We conducted a randomized,double-blind,placebo-controlled trial to investigate the preventive effect of the administration of the anxiolytic agent cloxazolam (3 mg/day) together with standard antiemetic measures (5-HT₃ receptor antagonist and dexamethasone) for nausea and vomiting in lung cancer patients undergoing chemotherapy with cisplatin (>60 mg/m²).Subjects were randomly assigned to a cloxazolam group and placebo group by the minimization method,and the preventive effects in each group were compared over 5 days of administration starting on the night before chemotherapy.The allocation conditions were psychological state of patients digitized using a self-rating depression scale,concurrent medications,presence or absence of nausea and vomiting before treatment,and sex.The severity of nausea was scored on a self-rating survey form for 7 days beginning on the day that chemotherapy was started,and the overall clinical effect was assessed on the basis of this score and the number of times patients vomited.Data were recorded for 38 subjects.
Nausea and vomiting were significantly inhibited in the cloxazolam group from Day 1 to Day 3 of administration.The cumulative total inhibition rate for nausea and vomiting during the protocol period was also significantly better in the cloxazolam group than in the placebo group.A stratified analysis of the relationship between the patient's psychological state and the antiemetic effect showed that the inhibitory effect of cloxazolam with respect to delayed nausea was significantly higher when the level of depression was low immediately before chemotherapy and when there had been a vomiting event during previous chemotherapy.

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A rapidly growing number of pharmacy graduates have been taking up employment as CRCs (Clinical Research Coordinators).In view of this,we think it is important to ensure that pharmacy students who engage in clinical trial work as a CRC take a curriculum that prepares them well for this profession.This is in keeping with“new five-year plan for clinical trial activation”which states that persons conducting clinical trials should be better qualified.
The curriculum should be improved not only from the point of view of the knowledge provided but also by including practical training in clinical trials in order to prepare students for their future work as a pharmacist by ensuring that they have a correct understanding of clinical trials.In order to make the part of the pharmacy curriculum on clinical trials more useful to students,we investigated the image that pharmacy students and health insurance pharmacy pharmacists have of clinical trials as well as clinical trial participation factors.
The pharmacists' image of clinical trials was more negative than that of the students,they had a strong feeling of anxiety towards them,and tended to be passive regarding participation in clinical trials.
We will use these results to examine the pharmacy education program in relation to clinical trials.

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The aim of this study was to clarify the influence of renin-angiotensin (RA) system blockers on the anti-cancer effect of chemotherapy with bevacizumab and its adverse effects.Twenty-six patients treated for metastatic colorectal cancer at Kyoto University Hospital between August 2007 and July 2008 were assessed.All of the patients received bevacizumab plus mFOLFOX 6 or FOLFIRI,and were divided into a control group (23 patients) and an RA system blocker group (3 patients).
Regarding background factors,which included chemotherapy doses,the only significant difference between the groups was with respect to age.However,hypertension grades in the RA system blocker group were significantly higher than those in the control group,and RA system blockers had no significant antihypertensive effect.There was no severe proteinuria in either group.As for anti-cancer effects,in the control group,6 patients exhibited a partial response and in 16 patients,the disease was stable.In only one patient was the disease progressive.On the other hand,the disease was progressive in all patients in the RA system blocker group.
These findings indicate that anti-hypertensive agents which provide better hypertension control than RA system blockers may be necessary as first line medication for the management of bevacizumab-induced hypertension.Although RA system blockers are useful antihypertension agents,they might not be able to control bevacizumab-induced hypertension and proteinuria,and could reduce the anti-cancer effect of bevacizumab.

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Progesterone (P) is an important hormone for the establishment of pregnancy,and its administration is useful against luteal insufficiency.In view of the problems with commercially available oral and injectable formulations,vaginal suppositories formulated in the hospital are used in the clinical setting.However,since the half-life of P suppositories is short,it is difficult to maintain constant blood concentrations.
We have been trying to develop effective sustained-release suppositories that maintain drug efficacy and prevent adverse effects by examining the extent that the release of the active ingredient is sustained for various suppositories.In the present study,we prepared 12 types of sustained-release suppositories containing P and 13 types of sustained-release granules containing P.There was sustained release of P from all of the suppositories,whose ranking according to degree of sustained release was almost the same as that of P from the granules.Among the suppositories with good sustained-release characteristics,we selected one for use in evaluating the plasma concentration of P in a healthy volunteer and were able to confirm that the blood P concentration was sustained to a greater extent than that for the conventional P suppository.

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In order to realize effective education concerning Kampo (Japanese traditional medicine),we administered a questionnaire survey to all pharmacists working in Tokushima Prefecture.The respondents were divided into 5 groups designated C1-C5,by cluster analysis based on their knowledge of Kampo.Clusters were characterized by comparing responses.
According to the results of our survey,around 50% of the working pharmacists came under groups C1 and C2.The members of these groups recognized the importance of“lifetime education”concerning Kampo but they did not have opportunities to obtain it.They were also aware that they were doing a poor job in dealing with Kampo.Group C2 had the greatest number of pharmacists in it and since they felt that they were poor in prescription analysis,lectures on unusual usage and the principles underlying them would be valuable.Further,such instruction should be carried out as soon as possible after graduation since there were so many young pharmacists in the C2 group.
As most of the pharmacists working in community pharmacies already had experience in compounding Kampo,they should be provided with lectures which include more advanced level information since they believed that they had a basic understanding of the meaning of Kampo prescriptions.
Awareness of Kampo differed by age group and by the types of facilities pharmacists worked in so it is important to match any practical educational program for them to their working situation.We would also like to emphasize the importance of Kampo education for undergraduate students.

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Diarrhea is a very common,important adverse effect associated with antibiotic therapy.For the prevention and treatment of diarrhea,Biofermin (BF) probiotic preparations are prescribed frequently and an antibiotic-resistant probiotic BioferminR (BFR) is particularly useful against antibiotic-associated diarrhea.BFR is often prescribed in combination with antibiotics to which the probiotic is susceptible or with off-label drugs such as anti-cancer drugs.
We investigated the concurrent usage of such probiotics and antibiotics and anti-cancer drugs using data from the database of a computer order entry system at the Tokushima University Hospital (April 2006 to March 2008),as well through the use of a questionnaire given to hospital doctors.The results of our study suggested that not all doctors had a sufficient knowledge of the usage of BFR when prescribing it.In routine pharmacy work,pharmacists should therefore actively question doctors concerning prescriptions they have written for the combination of BFR and off-label drugs to ensure the proper use of BFR and prevent the emergence of drug-resistant bacteria due to bacterial mutagenicity associated with antibiotics and anti-cancer drugs.

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