The pharmacokinetics (PK)/pharmacodynamics (PD) theory has attracted attention in the treatment of infectious diseases. Drug concentrations and effects vary among patients for any given dose. A goal of population PK and PD is to identify patient-specific factors, such as weight, age, creatinine clearance (CCR), and disease and determine their associations with the observed PK/PD differences. Once associated with differences in drug concentrations or response, these distinguishing factors may then be used to better individualize drug therapy.
This review summarizes our evaluation of the PK/PD analysis as follows:
1)We investigated the compatibility of various carbapenem antibiotics with nafamostat mesilate for severe acute pancreatitis (SAP). Biapenem and doripenem, which exert their effects in a time-dependent manner, can be infused for prolonged periods for the treatment of SAP and other severe infections.
2)The population PK on tazobactam/piperacillin (PIPC) was analyzed in Japanese patients with community-acquired pneumonia using the Nonlinear Mixed Effect Model version VI. Analysis using the one-compartment model yielded the following results for PIPC: total clearance (L/h) = 8.22 + (CCR - 71.4) × 0.0561, distribution volume (L) = 13.7.
3)We found a positive relationship between the decrease in serum potassium levels and the liposomal Amphotericin B (L-AMB) dose. Logistic regression analysis of this relationship revealed that serum potassium levels tended to decrease on Days 5 to 6 of L-AMB administration.

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A survey was conducted at five insurance pharmacies for four months to clarify how frequently patients taking antihypertensives brought the drug profile book to their pharmacy; how frequently they used stickers for the profile book; and the correlated factors thereof. Survey forms were distributed to patients taking antihypertensives. The main questions were: (1) Patient attributes, (2) Frequency of bringing the profile book to their pharmacy, (3) Frequency of using the stickers, (4) Whether the respondents knew the role of the profile book, (5) Where they learned about the role of the profile book, (6) What kinds of advantages they could identify about using the profile book, (7) Whether they thought the profile book was useful to them (sense of utility), and (8) The number of times they brought their profile book and used the stickers within the latest five pharmacy visits. Analysis of the data of 245 patients revealed correlations between three patient attributes, ie, female, later-stage seniors, and multiple combination, and frequency of bringing the profile book and frequency of using the stickers. Additionally, patients who had a stronger sense of the utility of the profile book and/or thought the profile book was more advantageous had a higher frequency of bringing the profile book and using the stickers. This indicates that pharmacists will need to provide a comprehensible explanation of the role and advantages of the profile book especially to patients who are male, younger than later-stage seniors, and who take three and under medications, in order to enlighten them further.

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In drug therapy, pharmaceutical interventions and continuous follow-up observation by pharmacists are extremely important. However, medication management sessions must be effectively conducted when there are large numbers of inpatients. We therefore conducted “medication administration guidance before or after breakfast or lunch” for some patients hospitalized in our hospital wards.
The number of medication management sessions increased from 41.9 to 185.4 sessions/month over an 18-month trial. The number of patients who received sessions increased from 29.3 to 89.0 patients/month. The number of sessions provided per patient increased from 1.42 to 2.09 times/month. The medication management guidance fee was increased from 524.3 to 762.9 points/patient. The rate of implementing the medication management session was 100%.
The number of medication management sessions and guidance fee were successfully increased by changing the time of management guidance. The results suggest the possibility of providing sessions for all patients in our hospital, providing interventions in the early stages, and offering safer and more effective drug therapies.

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To evaluate the economic impact of regimens including the oral anticancer drug S-1 (a combination of tegafur, gimeracil, and oteracil), we performed cost-minimization analysis to compare the medical costs of S-1 plus irinotecan (IRIS) with those of conventional intravenous treatment with oxaliplatin or irinotecan plus fluorouracil and folinic acid (mFOLFOX6/FOLFIRI) in patients with advanced colorectal cancer. Patients with advanced colorectal cancer were extracted from the ordering system database for outpatients in Showa University Hospital. Direct medical costs and patients' time-related costs were calculated from the hospital billing data and the average Japanese labor wage, respectively. The results were analyzed from a limited societal perspective. Twenty-nine patients with advanced colorectal cancer were identified, and 25 IRIS regimens, 11 mFOLFOX6 regimens, and 5 FOLFIRI regimens were registered. Mean (± SE) monthly costs of treatment were 183,682 (± 4,767) yen for IRIS regimens and 279,077(± 13,345) yen for mFOLFOX6/FOLFIRI regimens. The monthly cost of IRIS regimens was significantly lower than that of mFOLFOX6/FOLFIRI regimens (P < 0.0001). IRIS regimens are cost-saving compared to mFOLFOX6 or FOLFIRI regimens for the management of advanced colorectal cancer.

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Pharmacists who handle antitumor drugs are at risk of exposure when they prepare, administer and dispose of antitumor drugs. Although concern for surface contamination of antitumor drugs has gradually grown in Japan, which drugs are contaminated and to what extent have not been verified. In this study, we performed a questionnaire survey to clarify the actual state of occupational exposure for several pharmaceutical companies. We chose drugs frequently used in the National Hospital Organization, which could cause occupational exposure, and studied such antitumor drugs at the injection vial surface by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). We selected the following objects of drug vials; 5-FU, cyclophosphamide, gemcitabine, pemetrexed and paclitaxel as hazardous and frequently used drugs for chemotherapy. The surfaces of these drug vials were measured using LC-MS/MS under respective experimental conditions. The state of surface contamination varied by the respective drug vials. Most vials of cyclophosphamide and gemcitabine were contaminated by their contents, whereas the contamination of 5-FU and pemetrexed were detected only in several lots with very low amounts. Contamination by paclitaxel was not detected in any of the three lots. It is important to publicize the potential of contamination and an appropriate handling procedure to minimize exposure by antitumor drugs. Furthermore, pharmaceutical companies should supply safer products and play a more active role in the disclosure of information on their products.

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We carried out quantitative assessment of side effect management and pain control of pharmacist intervention for patients receiving outpatient chemotherapy. Between October 2011 and October 2012, total 3,444 chemotherapies were conducted at Shiga University of Medical Science Hospital. Of 331 chemotherapies, we intervened with side effect management, and calculated the improvement rate to compare the most severe grading of side effects or face scale (FS) between before and after pharmacist intervention. Of 331 interventions, 317 (95.8%) prescription suggestions were adopted by physicians, of which 266 were assessable for grading or FS. Of 266 assessable interventions, 135 suggestions (50.8%) caused significant improvement of the most severe grading score or FS, as compared to before pharmacist intervention. Improvement rate including patients' subjective symptoms was 69.5%. The results of our study indicate that side effect management and pain control by pharmacist intervention could be useful for grading improvement of receiving outpatient chemotherapy.

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Opioid usage in cancer treatment is low in Japan compared with Western countries. One reason for this is that Japanese patients have misconceptions about and are reluctant to receive administration of opioid analgesics. Dispellingthese misconceptions could contribute significantly to improving the quality of life (QOL) of cancer patients. To elucidate the factors behind these misconceptions, we decided to investigate the factors affecting the misconceptions and usage of opioid analgesics in the public. A questionnaire survey was conducted on drugstore visitors in their forties, fifties, and sixties. The questionnaire consisted of 29 items that aimed to determine the level of misconceptions about and resistance to receiving opioid analgesics, as well as the factors related to the misconceptions. The results were analyzed via factor analysis and structural equation modeling analysis (SEM). Factor analysis revealed the following as factors related to misconceptions about opioid analgesics: “attitude to endure the pain of cancer,” “resistance to the use of medication,” “lack of trust in healthcare professionals.” “The lack of trust in healthcare professionals” affected misconceptions about opioid analgesics, whereas “resistance to the use of medication,” “attitude to endure the pain of cancer” affected misconceptions about opioid analgesics indirectly as derived by SEM (GFI = 0.907, AGFI = 0.863, RMSEA = 0.053). The results of this study suggest that it is important to take measures to reduce misconceptions about opioid analgesics.

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Colestyramine and colestimide have been utilized for lowering serum cholesterol levels in patients with dyslipidemia. They cause drug interactions of different extents, with colestyramine decreasing the absorption of various anionic drugs more potently than colestimide. However, the factors behind the differences in their drug interactions have not yet been fully characterized. We previously reported that colestimide has greater ability than colestyramine to adsorb phosphate. In the present study, we evaluated the binding characteristics of colestyramine and colestimide to several anionic drugs in the absence or presence of phosphate. Resin suspension and drug solution were prepared using ultrapure water, the Japanese Pharmacopeia (JP) 1^st fluid or JP 2^nd fluid for dissolution testing. After addition of the drug solution to the colestyramine or colestimide suspension, the mixture was gently shaken for 30 min at room temperature and then subjected to high-speed centrifugation. The drug concentration in the resultant supernatant fluid was determined by HPLC. When using ultrapure water as a medium, a much greater level of ibuprofen binding was observed for colestimide than for colestyramine. However, when using the JP 2^nd fluid as a medium, almost negligible binding occurred between ibuprofen and colestimide whereas no inhibition of ibuprofen binding to colestyramine was observed. Warfarin, indomethacin, diclofenac, and taurocholic acid showed similar tendencies to ibuprofen. The present results strongly suggest that the much greater interaction of phosphate with colestimide than with colestyramine in the gastrointestinal tract is a possible factor for the weaker drug interactions of colestimide than colestyramine.

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Light emitting diodes (LEDs) are widely used in lighting applications. In this study, we examined the differences in the degree of the color change of various medicines between LED lighting and fluorescent lighting. The degree of the color change of the medicines was evaluated subjectively, by the observation of the evaluator, as well as objectively, using a colorimeter. Noticeable color changes were observed in the Lasix^® 20-mg Tablet(Tab), Fluitran^® 2-mg Tab, and Phenobal^® powder after exposure to either LED lighting or fluorescent lighting. Interestingly, the color change of the Lasix^® 20-mg Tab was smaller for the LED lighting than for the fluorescent lighting.

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