Voriconazole (VRCZ) is a triazole antifungal agent that exhibits large inter-individual variability in plasma concentration. Reasons for this include non-linear pharmacokinetics due to its saturated metabolism and genetic polymorphism in CYP2C19. Because VRCZ has the potential to produce adverse reactions such as hepatotoxicity and visual disturbances, therapeutic drug monitoring is required to optimize treatment. Therefore, this study aimed to evaluate the predictive performance of published population pharmacokinetic (PPK) models of VRCZ. Demographic and laboratory data were retrospectively collected from the medical records of 39 patients who underwent VRCZ treatment. Patients were classified into lower and higher concentration groups by visual inspection of observed weight- and dose-normalized trough concentration. We assumed that the patients in the lower concentration group were more extensive metabolizers of CYP2C19 versus patients in the higher concentration group. We calculated PPK-predicted concentrations of VRCZ for each patient after taking the estimated genotype into account. Next, we examined their predictive performance by calculating the mean prediction error (ME), mean absolute prediction error (MAE), and root mean squared error (RMSE). Thirty and 9 patients were included in the lower and higher concentration groups, respectively. The predictive performance of the PPK model constructed from a Japanese phase Ⅲ study was significantly smaller than that from the other PPK studies (r = 0.868 vs 0.694, P = 0.001; ME －0.27 µg/mL, MAE ＋0.90 µg/mL, and RMSE ＋1.15 µg/mL for the Japanese PPK model). Finally, we constructed a suggested VRCZ safe dose schedule. Our findings provide useful information for adjusting the VRCZ dosage to improve clinical safety and effectiveness.

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There is little information on sedimentation time of glass pieces in glass ampoules. In this study, we predicted the sedimentation time of glass pieces in commercial injections using Stokes equations. First, we measured the viscosity and density of 21 types of commercial injection. The viscosity of injections changed largely with temperature, and the higher viscosity showed a longer predicted sedimentation time. Moreover, considering factors such as storage temperature and the height from bottom to surface of injections, the predicted sedimentation times of glass pieces was long, that is 3.9-19.0 min/ampoule at 20°C. These results suggest the risk of mixing glass pieces in parts of commercial injections.

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Although the loading dose (LD) for teicoplanin is required, the appropriate regimen is a matter of debate. This study estimated the LD by revising its central compartmental volume of distribution (Vc) in the population pharmacokinetic (PPK) parameter, which is frequently used for Japanese patients.
This was a retrospective study. Thirty-six patients who were administered teicoplanin and underwent serum trough level measurement within 48 hours were eligible. We compared the measured and predicted levels using the PPK parameters and estimated the mean prediction error (ME, μg/mL) and the mean absolute prediction error (MAE, μg/mL) for prediction. We revised the Vc value of the PPK parameter (10.4 L) to achieve the ME of 0, and denoted the revised Vc as rVc, which was then validated for other groups of patients by comparing measured and predicted steadystate serum trough levels (Css). We subsequently estimated the LD that can achieve a serum trough level between 15 and 30 μg/mL 48 hours after beginning administration.
The rVc was estimated to be 6.6 L, and the MAE was significantly decreased from 4.0 to 2.9 (P<0.05) by using rVc. We demonstrated that the rVc could also be used for predicting Css. The LD was estimated to be 600 mg q12h × 4 for 2-days loading and between 800 mg and 1000 mg q12h × 2 for 1-day loading.
This study estimated the LD for teicoplanin, demonstrating that it is useful to estimate individual LD based on PPK parameters.

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Medicinal carbon (MC) granules were prepared by the wet granulation method (wet mass extrusion) using carboxymethylcellulose sodium (CMC-Na) as a binding agent. In addition, croscarmellose sodium (CC-Na) was used as an additive at 0 - 10% (w/w) to MC. The obtained granules were examined in vitro for the physical strength, disintegration properties and adsorption characteristics. From friability tests, all the granules had good strength. They slightly disintegrated in the disintegration test with water for 30 min, but the addition of CC-Na significantly reduced the granule weight after the disintegration test. It was suggested that the addition of CC-Na should facilitate water immersion and consequently cause components such as CMC-Na or CC-Na to be lost partially; though such changes in the physical state could not be discernible to the naked eye. In adsorption experiments using acetaminophen solution (0.6 mg/mL), the adsorption capacity was almost retained in all the granules. Although the adsorption rate of the granules without CC-Na was fairly slower than that of MC powder, it was significantly improved by the addition of the CC-Na at 4 and 10% (w/w). In particular, the granules with CC-Na at 10% (w/w) displayed 65% (w/w) of saturated adsorption with a small coefficient of variance (<7%) at 20 min after the start of the adsorption test. Thus, since the MC granules with CC-Na at 10% displayed good physical strength, high adsorption capacity and a fairly fast adsorption rate, they are suggested to be useful as a compact MC dosage form.

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The dissolution rate control of nateglinide from matrix granules was investigated under a sink condition. Nateglinide/hydrogenated castor oil (HCO) matrix granules showed pH dependent dissolution profiles. By adding calcium chloride (CaCl₂) to nateglinide/HCO matrix granules, the pH dependence of the dissolution profile was reduced. Furthermore, it was confirmed that the nateglinide/HCO matrix granules containing CaCl₂ decreased both postprandial blood glucose level and fasting blood glucose level in normal beagle dogs. These findings are considered to be useful in order to design a nateglinide sustained release formulation.

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To ensure disaster preparedness, pharmacists must be familiar with extraordinary disaster response practices in advance of a disaster, particularly in communities with a high rate of separation between dispensary and medical practice and with many patients with chronic diseases who may be without prescriptions following a disaster. To make future improvements to responsiveness, we investigated community pharmacies' awareness of extraordinary measures following a disaster and relations between such awareness and the implementation of disaster prevention measures or business operation systems. Self-administered questionnaires were distributed to all 526 pharmacies in Akita prefecture. Obtained data were analyzed by χ² analysis and Fisher's exact test. More than 80% of respondents were aware of special handling of prescription drugs and insurance dispensing at a time of disaster; this high awareness was largely due to the Great East Japan Earthquake, and possibly because Akita is close to the disaster area. Awareness may not be as high in areas farther from the disaster area. Only 43% of pharmacies stored a printed version of “The Disaster Preparedness Manual for Pharmacies and Pharmacists”, specifying extraordinary measures at the time of a disaster. As approximately 80% of respondents answered they could act after having “reconfirmed the contents of the manual”, we recommend a printed version be stored at every pharmacy so information is readily accessible even during a power outage. Pharmacies that have expanded business into other prefectures tend to have better disaster preparedness. Each community should develop an appropriate disaster-prevention system so even small pharmacies can establish disaster preparedness.

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We conducted a training program at a pharmacy school to enhance students' understanding of the characteristics and roles of generic drugs. The program reviewed the quality (4 evaluation items), formulation properties, information delivery systems, drug supply systems (4 evaluation items), and patient's copayment for four types of formulations, each with brand-name and generic versions. This study evaluated the students' cognitive changes in regard to generic drugs and analyzed factors influencing these changes as well as the students' satisfaction with and opinions about the usefulness of the training. A questionnaire was distributed to 158 students who participated in the program in 2011, and 151 fully completed questionnaires were analyzed using regression analysis. Results indicate that the training program enhanced the students' interest in generic drugs. Of the evaluation items mentioned above, bioequivalence, name and appearance, drug adjuvant, formulation properties, and listing in the Japanese version of the Orange Book were positively correlated with understanding of generic drugs by using regression analysis. These findings suggest that the program was useful in increasing the students' understanding of the characteristics and roles of generic drugs. This was also considered to lead to a better ability to choose the appropriate drugs based on patients’ needs and usability.

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