In clinical monitoring, we have sometimes observed blood pressure elevation in patients undergoing FOFOX/FOLFIRI therapy for colorectal cancer at Tottori University Hospital. Therefore, we retrospectively investigated the occurrence of blood pressure elevation using our hospital’s information system. A difference in systolic blood pressure between before and after FOLFOX/FOLFIRI therapy of more than 20 mmHg, was defined as blood pressure elevation for this study.
Between April 2005 and March 2009, a total of 43 patients underwent more than 5 courses of FOLFOX/FOLFIRI therapy. Blood pressure elevation was observed in 10 of these 43 patients (23.3%) and it occurred both in patients receiving FOLFOX (n=7, 17.1%) and those receiving FOLFIRI (n=3, 14.3%). We then examined the findings for an association between blood pressure elevation and clinical characteristics of patients. There was no significant difference in the dose intensities or cumulative doses of the anticancer agents constituting FOLFOX/FOLFIRI therapy between patients with blood pressure elevation and those without. There was therefore no clear cause of the blood pressure elevation observed in patients who underwent FOLFOX/FOLFIRI therapy. However, physicians should carefully monitor changes in blood pressure and other basic vital signs in order to prevent a reduction in treatment options due to hypertension.

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In order to contribute to antimicrobial stewardship, it is extremely important for pharmacists to apply PK / PD theory (combination of pharamacokinetics (PK) and pharmacodynamics (PD)) as well as the montecarlo simulation. However, very little useful PK / PD simulation software incorporating the montecarlo simulation is available for the clinical setting. We therefore developed easy-to-use software for this purpose based on Microsoft^® Office Excel.
With it, drug clearance, volume of distribution, and PK / PD parameters are easily calculated using correlation equations derived from patient parameters, such as serum creatinine level and body weight, based on population pharmacokinetic parameters reported by various researchers. The montecarlo simulation is performed by generating pseudorandom numbers based on antibiograms, or interindividual coefficients of variation for each population pharmacokinetic parameter. We found that population pharmacokinetic parameters reported as following a 2-compartment model could be used as a 1-compartment model in the montecarlo simulation and report for the first time that the RN method (consisting of the RAND function and NORMSINV function in Microsoft^® Office Excel) can be utilized as a pseudorandom number generator in the same manner as the MB method (consisting of Mersenne-Twister method and Box-Muller method).
Adoption of this software in the clinical setting will enable us to evaluate individual patient PK / PD parameter values and contribute to providing useful evidence for PK / PD theory.

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A 40-year-old woman who had received warfarin potassium (3 mg/day) for deep-vein thrombosis was diagnosed with atypical mycobacteriosism, and concomitant administration of rifampicin, clarithromycin and ethambutol was commenced. The PT-INR of this patient, which had been maintained at around 2.0, was found to have markedly decreased 9 days after beginning co-administration of warfarin and the anti-mycobacterium drugs, suggesting rifampicin induced warfarin metabolism, which is well documented. In view of the decrease in PT-INR, the warfarin dosage was increased up to 5.5 mg/day to attain a PT-INR level in the therapeutic range, but this did not alter the level.
Rifampicin was changed to rifabutin since drug-drug interaction is considered to be generally less severe than with rifampicin. However, as there had been no increase in PT-INR, the administration of rifabutin was ceased. A rise in PT-INR was observed 17 and 31 days after the withdrawal of the rifabutin and rifampicin, respectively.
Warfarin is known to be metabolized by cytochrome P450 (CYP) isoforms 2C9 and 3A4 and rifampicin has been reported to be a potent inducer of CYP3A4 and 2C9. Although rifabutin has the ability to induce CYP3A4, there have been few reports of drug-drug interaction with warfarin. However, the current case provides the first evidence for rifabutin exerting an influence on warfarin metabolism.
In conclusion, our findings suggest that not only rifampicin but also rifabutin induce warfarin metabolism and that its pharmacological effects could be attenuated when combined with these drugs.

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Many hospitals have cancer chemotherapy review committees to evaluate the validity of chemotherapy regimens from the medical and pharmaceutical perspectives, and pharmacists play an important role in these committees. However, proper evaluation of regimens depends on the experience and knowledge of pharmacists. In the present study, we developed various support tools for this purpose and standardized the procedure for evaluating chemotherapy regimens to make it more dependable and efficient. The tools included a regimen check sheet, a flowchart for information retrieval, a flowchart for evidence-level retrieval and a literature check sheet.
The usefulness of the support tools was verified by having pharmacists with little experience of cancer chemotherapy use them. Doing this improved the pharmacists’ ability to evaluate the FEC regimen as well as their knowledge of chemotherapy. The standardization of procedures using support tools is very useful to the evaluation of chemotherapy regimens.

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In this study, we investigated the current status of health instruction for patients with chronic illnesses by surveying community pharmacies with the objective of determining new ways of promoting health guidance. A total of 564 pharmacies randomly sampled from among 5640 pharmacies in the Tokyo metropolitan area were surveyed by telephone from May 19 to 30, 2008. The response rate was 56.6% (n=319).
The results revealed that 88.4% (282) provided health consultation and guidance regarding diet and exercise, and 60.2% (189) provided advice on matters other than those related to the use of drugs. Compared with pharmacies that only provided consultation regarding the use of drugs, those which gave advice on other matters as well had higher scores for staff registered for training courses (64.0% vs. 38.7%), use of manuals (31.2% vs. 22.6%), provision of instruments for determining general health status, such as those for blood pressure and blood glucose level measurement (65.1% vs. 51.6%), and sale of such instruments (52.4% vs. 34.4%). The most widely provided instruments were those for blood pressure measurement (108 pharmacies) and clinical thermometers (65 pharmacies).
Although many pharmacies were playing a role in primary care, we speculated that there was variation in the content of health guidance and methods of providing it because of the infrequent use of manuals. Therefore, we recommend that pharmacy consultation services be standardized.

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We take measures to prevent the recurrence of aspiration pneumonia at Yokkaichi Municipal Hospital. However, as the effectiveness of these measures varies among patients, we examined factors that might contribute to aspiration pneumonia recurrence.
Patients with recurring aspiration pneumonia were more frequently prescribed agents that might reduce aspiration function (41.7%) compared to patients that were not prescribed these agents (5.2%; p=0.02) and their serum albumin levels were significantly lower (2.7±0.6 g/dL vs. 3.1±0.5 g/dL; p<0.01). Additionally, for those with serum albumin levels <2.5 g/dL, the frequency of prescribing such agents was significantly higher (50.0%) than those with serum albumin levels >2.5 g/dL (10.5%; p=0.03).
Based on these results, in order to prevent the recurrence of aspiration pneumonia, we recommend the cessation of agents that might reduce aspiration function or their replacement. Improvement of hypoalbuminemia is also necessary.

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When lansoprazole orally dispersing tablets (30 mg) are administered through a tube, a residue often remains in the syringe and tube because the tablets contain fine enteric granules which are nearly insoluble in water. As a solution, we added thickening agents and examined their effectiveness in reducing the residue in syringes.
The amount of lansoprazole residue in syringes was 11.4±1.3 mg when the agents were not added (Group A) and 1.3±0.6 mg when the agents were added (Group B). For Group A, the residue from a single injection was approximately 30-40% of the total amount of lansoprazole, while there was almost no lansoprazole residue for Group B. Performed by nurses, tube administration took slightly longer for Group B - 51.4±5.5 sec for Group A and 70.8±6.1 sec for Group B.
Our solution of just adding thickening agents improved the dispersivity of the drug in the suspension as well as the mobility of the drug suspension, by getting the particles and solvent traveling at the same speed. It enabled injection to be performed smoothly and decreased the amount of residue in the syringe. The addition of thickening agents is therefore useful in tube administration because avoiding any lansoprazole loss would help ensure that the expected efficacy is achieved, since this is dosedependent.

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We conducted a survey on pharmaceutical counseling at hospitals in the Kyushu-Yamaguchi Area to investigate problems in the management of inpatient pharmaceutical care. The implementation rate of pharmaceutical counseling was 81.3%, and was steadily increasing. Although the implementation rate for checking medicines brought by patients at the time of hospitalization was also high (96.2%), pharmacists expressed dissatisfaction with the present situation. The results indicated that continual, efficient assessment of medicines brought by patients when hospitalized would lead to an increase in pharmaceutical care fees reimbursed by health insurance.
Respondents said that they provided continuous pharmaceutical counseling regarding the management of medicines brought in by the patients, but their scores for satisfaction with the current situation in the self-assessment varied depending on whether they provided pharmaceutical counseling when the patients left hospital or not. The satisfaction scores suggested that hospital pharmacists wished to provide pharmaceutical care consistently from the time of hospitalization until after the patients left hospital.
A lack of pharmacists is hindering the provision of pharmaceutical counseling in many hospitals and based on our survey results, we believe it is important to increase the amount of technical fees received for pharmaceutical counseling conducted when patients are discharged. We also feel that promoting cooperation between hospital and community pharmacists would help further improve pharmaceutical care.

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