Silodosin is a potent selective α _1A-adrenoceptor antagonist used for the treatment of lower urinary tract symptoms associated with benign prostatic hyperplasia (BPH).In the present study,we conducted a population pharmacokinetic (PPK) analysis using silodosin plasma concentration data obtained in a Phase III long-term study in order to evaluate the pharmacokinetic characteristics of silodosin in patients with BPH.In this study,we analyzed 1,553 samples taken at the steady state following repetitive oral administration to 258 patients based on a nonlinear mixed effects model according to a onecompartment model which was parameterized in terms of oral clearance (CL/F) and apparent volume of distribution (V/F).In the PPK analysis,the effects of age,serum creatinine,alanine aminotransferase (ALT),C-reactive protein (CRP),and concomitant substrates or inhibitors of CYP3A4 on the pharmacokinetics of silodosin were evaluated.
The results suggested that age,ALT and CRP affected both CL/F and V/F of silodosin,and that serum creatinine affected CL/F.Both CL/F and V/F decreased with an increase in these covariates.On the other hand,the concomitant substrates or inhibitors of CYP3A4 were not significant covariates for CL/F.Among these factors,ALT had the most significant effect on plasma silodosin concentration.For example,after repetitive oral administration,the trough concentration for patients with an ALT value of 82.6 IU/L was 2.45 times higher than that for patients with an ALT value of 22.6 IU/L.These results indicate that liver function and CRP affect the pharmacokinetics of silodosin,and the effect of liver function is the most significant.

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Conscious young adult male rats were given total-parenteral nutrition (TPN) with or without a soybean fat emulsion for 4 days and those that did not receive the emulsion (fat-free TPN group) developed severe fatty liver with hyperglycemia,hyperinsulinemia,and hypotriglyceridemia.These disorders were improved by administering TPN supplemented with soybean fat,equivalent to 20% of total calories,with glucose correspondingly reduced.In the fat-free TPN group,the expression of sterol regulatory element binding protein 1c (SREBP1c),acetyl-CoA carboxylase (ACC),and fatty acid synthase (FAS) mRNAs in the liver were coordinately up-regulated,resulting in an increase in non-essential fatty acids and a decrease in essential fatty acids in the liver,due to the fat supply drying up.In contrast,expression of carnitine-palmitoyltransferase (CPT) 1a mRNA decreased.However,in the group given the fat emulsion in their TPN,the expressions of all of the above types of mRNA remained similar to those in an oral diet control group.
It appeared that the hyperinsulinemia following infusion of excess glucose had induced lipogenesis and a decrease in fatty acid β-oxidation in the liver and that these changes were prevented by supplementation of soybean fat equivalent to 20% of total calories (with a corresponding reduction in glucose).Therefore,it may be appropriate to routinely supplement fat-free TPN with soybean fat in the clinical situation,substituting it for part of the glucose.In addition,serum glucose and insulin levels should be monitored during TPN infusions.

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To promote the proper use of voriconazole (VRCZ),we monitored VRCZ blood concentrations,and investigated the clinical significance of doing this.On comparing C/D (blood VRCZ concentration/VRCZ dose) values for different VRCZ administration methods we found that there was no significant difference between the intravenous drip and oral administration methods (t-test : P=0.607)in this respect.There was also no correlation between the dose of VRCZ per unit body weight and its blood concentration (variance analysis : R²=0.012,P=0.449).Though total bilirubin (T-Bil) levels were correlated with C/D values (variance analysis : R²=0.104,P=0.020),serum creatinine clearance (CCr) and C/D values (variance analysis : R²=0.062,P=0.078)were not correlated.Furthermore,C/D values in males were significantly higher than those in females (t-test : P=0.001).
Approximately 25% of the patients had a blood concentration trough value exceeding 4.5μg/mL,which indicates an enhanced risk of liver dysfunction,and this suggests that the measurement of blood VRCZ concentrations is clinically important for preventing side effects.

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The objective of our study was to investigate the current status of the use of green leaf juice (GLJ ; made from kale,young barley leaf etc) among consumers and patients visiting drugstores,with regard to reasons for using GLJ,overall perception of safety and efficacy of GLJ,and the need for information on such dietary supplements.Between February and March 2006,a total of 563 consumers and patients visiting 68 drugstores owned by Tsuruha Inc.,in Hokkaido,Tohoku,and Kanto districts completed the questionnaire.The results showed that GLJ use was substantially higher among elderly people (65 years old and above) and people under long-term treatment with antihypertensives,antiallergics or antidiabetics.Though 33.2% of GLJ users thought it was effective,55% were uncertain about its effectiveness.Adverse events had been experienced by 2.4% of GLJ users.Other findings were that 55.5% of the respondents were taking GLJ daily and 27% had not read the precautions in the package insert.
The present investigation showed that the major users of GLJ were elderly persons (of 65 years and above) who were taking medications.It is thus important for medical staff to routinely ask such patients if they are using any dietary supplements in order to collect evidence for their potential benefits or harm they could do,and to provide information on them in consideration of differences in literacy levels.

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We prepared guidelines whose aim was to enable pharmacists to provide instruction on the use of dietary supplements easily based on scientific evidence.As a result of comparing various databases of scientific information on dietary supplements,we felt that the National Institute of Health and Nutrition database was the most suitable due to the large number of supplements listed in it,wide variety of information,and the fact that it was up-to-date with the market situation.However,on investigating the efficacy of 36 supplements receiving attention on the internet,the database only contained scientific evidence on 12 of them and 7 of these supplements had specified uses in health management.It thus seems that there is insufficient evidence for the efficacy of many supplements searched on the internet.
In order to provide appropriate guidance on dietary supplements,in addition to scientific evidence of efficacy,we considered that 4 other criteria should be used to evaluate supplements : 1)possibility of interactions with medication,2)quality of dietary supplement,3)seriousness of disease and 4)psychological reliability of the patient taking the dietary supplement (positive placebo effect).Based on these 5 criteria,our guidelines should enable pharmacists to provide patients with instruction on dietary supplements more easily and accurately.

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To evaluate combination therapy with warfarin potassium (WF) and bucolome (BUC),we assigned patients on warfarin potassium (WF) at Kochi University Medical School Hospital to a group also receiving BUC (BUC-combination group) and a group not receiving BUC (non-combination group),and compared the WF doses and TT values.In each patient,we investigated the doses of WF before and after the start or discontinuation of combination therapy with BUC.There was no significant difference in TT values between the two groups.However,the WF dose in the BUC-combination group was significantly lower than that in the non-combination group.BUC was therefore useful for maintaining anticoagulation activity and decreasing the dose of WF.Furthermore,there was a correlation between the doses of WF before and after the start or discontinuation of combination therapy with BUC in each patient.Based on the regression line obtained using WF doses,in the presence and absence of BUC,the subsequent dose of WF could be predicted at the start or discontinuation of combination therapy with BUC,suggesting that it would be useful in anticoagulation control.

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We analyzed the clinical efficacy and safety of treating MRSA infections with high-dose teicoplanin (TEIC) (800 mg×2 on the first day and 800 mg/day on the following 6 days) and devised a method of predicting serum trough concentrations on the 8th day of administration.Serum trough concentrations were obtained on the 1st day (day 1 ; D1),2nd day (day 2 ; D2),4th day (day 4 ; D4)and 24 hrs after the 7th day of administering TEIC (day 8 ; D8).We also compared the predicted D8 trough concentrations,based on those at D2,D4 and D2 and 4 using a Bayesian method based on the population pharmacokinetic parameters in TEICTDM Ver.2.0,with the actually measured trough concentrations on D8.
The results were as follows : 1)The trough concentrations of TEIC on D2,D4 and D8 were 17.1±6.0,18.0±6.3 and 20.8±7.1(mean±SD)μg/mL,respectively ; 2)High-dose treatment with TEIC achieved the effective serum trough concentration (15μg/mL) on day 2,and this treatment method demonstrated clinical and bacteriological efficacy and safety ; 3)Predicted concentrations on D8 calculated from either D2 or D4 levels were 75% and 35% higher than the observed values (p <0.001),respectively,but there was no significant difference when predicted concentrations at D8 were calculated from both D2 and 4.
In the present study on treatment with high-dose TEIC,when the Bayesian method was applied,a single sampling point produced low-reliability pharmacokinetic values with large prediction errors,while the use of two sampling points made it possible to predict trough levels with considerable precision.

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Accidents due to the use of medicines brought to hospitals by inpatients have been reported and hospital pharmacists are required to manage the risks associated with such medicines.Many hospitals have recently introduced the Diagnosis and Procedure Combination with the objective of standardizing hospital treatment though most elderly inpatients have complications in addition to underlying diseases.We started to manage the medicines brought to our hospital by inpatients in July 2005.In this work,we have been checking the medicines brought to our hospital by inpatients,and have provided up-todate inpatient medication histories and drug information to doctors and nurses.By checking the medicines brought to our hospital by inpatients,we have been able to prevent the administration of contraindicated drugs,the unnecessary duplication of drugs and drug interactions.Our activities have also enabled inpatients to continue take medication safely for their complications after hospitalization,and drug costs to be kept down.

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Our hospital has adopted a system under which externally dispensed prescriptions are checked by the pharmaceutical department prior to delivery to patients.However,external prescriptions have created additional work for us in that we have to respond to inquiries from insurance pharmacies on doubtful points that remain in such prescriptions.We examined such inquiries received from June 1998,when externally dispensed prescriptions started to be issued,to August 2006 with regard to content and time based on entries in a record book,and assembled the data obtained for the purpose of studying the introduction of an ordering system linked to electronic patient records.As a result,we found that the number of inquiries on doubtful points was proportional to the number of externally dispensed prescriptions,and the time required for responses depended on the number of inquiries rather than the content of the inquiries concerning doubtful points.The average inquiry rate was 1.26% of the number of externally dispensed prescriptions issued by our hospital,a lower rate than that found in large-scale surveys,suggesting that our checks prior to delivery of prescriptions were effective.Furthermore,in consideration of efficiency and safety,responses by our pharmaceutical department to inquiries were considered to be necessary even after computerization.

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We improved the universal training model that had been used for bedside training at the School of Pharmaceutical Sciences,Kyushu University of Health and Welfare,making it into a pharmaceutical universal training model for checking various administration routes.The advantages of the model are as follows : (1)various gastric tubes can be inserted into gastric and intestinal fistulae ; (2)training on more organs is possible ; (3)suppositories can be simply inserted ; (4)easy to change bedsore pads,and (5)puncture site facilitates the checking of subcutaneous,intramuscular,and intravenous injections and intravenous hyperalimentation.
We conducted a questionnaire survey of students regarding the following points before and after the training : checking of various administration routes (tubal feeding,injection routes),practice in rectal administration to patients,bedsore care procedures and drug selection based on bedsore stage.Since there was a significant increase in the recognition of the necessity of these items and students understanding of them (p<0.01),we consider that the introduction of the pharmaceutical universal training model in clinical pharmacy training for pharmacists will improve their skill and ability to determine the best way of using drugs in treatment.

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We determined the adhesion loss in a metering glass for 9 types of syrup for infants,and investigated the relationship between the adhesion loss and the rheological properties of the syrups.There was a good correlation (r²=0.981)between the viscosity of the syrups and percentage syrup residues on the metering glass.Further,from the viewpoints of accuracy and efficiency in dispensing,our finding that percentage residues for a dispenser were much lower (<0.15%) than for the metering glass suggested that it was better to use a dispenser for dispensing viscous syrups with a viscosity of at least 50-60 mPa·s.The results of our examination of syrup viscosities in the present study are expected to be useful information for their administration,and to contribute to the establishment of dispensing procedures based on scientific evidence.

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For tube administration of tablets and capsules,the simple suspension method has been developed in which tablets or capsules are allowed to directly disintegrate and become suspended in hot water (55°C).In the present study,we focused on generic drugs,which have been increasingly used in recent years,and investigated the recovery of pravastatin after suspending generic and original brand-name drugs using the simple suspension method.
The results showed that the original drug disintegrated and became suspended in hot water within 10 minutes,with no problems regarding tube passage and recovery of almost 100% before and after tube passage.In contrast,among generic drugs,two tablets failed to disintegrate and become suspended within 10 minutes.When these tablets were crushed in advance,no problems were observed regarding tube passage,and recovery was almost 100% before and after tube passage.These results confirmed the validity of simple suspension method for pravastatin tablets with regard to both drug stability and the amount actually administered to patients.However,because certain generic drugs differed from the original drug in terms of disintegration and suspension,caution must be exercised when replacing original drugs with generic drugs during application of the simple suspension method.

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To clarify the factors in preference for insulin injectors,69 subjects (aged 20-49 years) were asked to select 1 of 4 different injectors and then to complete a questionnaire regarding 9 selection factors regarded as important,among them“ease of gripping”and“portability”,before and after instruction on operating the injectors.
“Portability”was considered the most important factor for selecting injectors on first impression,i.e.before instruction,and the percentage of subjects choosing“simplicity of operation”increased after instruction.About half of the subjects selected a different injector before and after instruction,so there appeared to be a relationship between injector selection and the evaluation factors.From the results,we made a table which we thought would be helpful in selecting insulin injectors based on factors regarded as important when using them in practice.

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Flushing is performed mainly to avoid compositional changes in the flow passage when drugs are administered by the I.V.push or piggyback infusion methods.This is done by injecting rinsing solutions,such as physiological saline or glucose solution,through side tubes before and after administration of drugs to dilute or replace them in the flow passage.In this study,we examined the flushing conditions for phenytoin sodium injection (Aleviatin^® injection) and the effect of its viscosity on flushing.Aleviatin^® injection is highly viscous and there is a high risk of compositional changes with it.For effective flushing,we found that the flushing volume depended on the volume of the tube and that it was necessary to use a volume of 15mL to 40mL of the rinsing solution.It was also noted that the viscosity of the injection solution affected the effectiveness of flushing.

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