The pharmacokinetic parameters of vancomycin have been much reported on.In order to plan initial dosage regimens precisely,we retrospectively investigated the predictive performance of pharmacokinetic parameters reported by Winter,Matzke,Grasela,Ducharme,Rodvold and Yasuhara and parameters for Japanese included in TDM analysis support software (Japanese parameters).We also investigated the propriety of amending serum creatinine concentrations (Scr).Amending Scr based on the Japanese parameters from under 0.6 mg/dL to 0.6 mg/dL gave the best predictive performance for patients overall.Regarding sex and age,amendment based on Matzke’s parameters for male patients under 65 produced good predictive performance and Yasuhara’s parameters achieved good predictive performance for male patients over 65.Amendment based on Rodvold’s parameters for female patients under 65 and that based on the Japanese parameters for female patients above 65 gave good predictive performance.Thus in the initial dosage regimen,VCM parameters that gave good predictive performance differed by age and sex and Scr.We also showed that it was useful to amend Scrs of under 0.6 mg/dL to 0.6 mg/dL in the revision.It is therefore possible to precisely plan initial dosage regimens using VCM parameters that are suitable for each patient.

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The association of disease stage and response with survival following treatment with 5-fluorouracil/cisplatin-based chemoradiotherapy (CRT) was evaluated in 51 Japanese patients with esophageal squamous cell carcinoma (ESCC).One course of treatment consisted of protracted venous infusions of 5-fluorouracil (400 mg/m²/24 h for days 1-5 and 8-citation=12)and cisplatin (40 mg/m²/3 h on day 1 and 8),and radiation (2 Gy/day on days 1-5,8-12 and 15-19),and a 2 nd course was given after a 2-week interval.The response was assessed about 4 weeks after the CRT by endoscopy,and chest and ab- dominal CT scans.The CR+PR rate was 80%,which was consistent with other institutions,and we confirmed that this CRT procedure was effective even for Stage III ESCC.The 2-year survival rate was 52%,which was comparable with or better than other institutions.Our results also showed that survival depended on the disease stage (p=0.027,Log-rank test).The response (CR or non-CR) was also associated with survival (p<0.0001,Log-rank test) with 2-year survival rates of 88 % and 13% for CR patients and non-CR patients,respectively.Overall,we concluded that the prognosis could be predicted from the disease stage or response,hopefully with good accuracy.

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Though N-acetylcysteine (NAC),an antioxidant,has been used to prevent radio-contrast-induced nephropathy (RCIN),the effectiveness of using it remains unclear as the results of studies regarding its protective effect have been inconsistent.Since oral solutions of NAC have an unpleasant smell and taste,we previously developed a jelly preparation of NAC and in the present study,conducted a questionnaire survey to evaluate its user friendliness.The results of the survey indicated that the jelly preparation was effective in masking the unpleasant smell and taste.We also retrospectively examined the effectiveness of NAC in protecting against RCIN.Sixteen percent of patients in our control group (n=81,no NAC) developed RCIN,whereas none of the patients in the NAC-treated group (n=67)developed it.RCIN was defined as a greater than 25% increase in serum creatinine level occurring within 48 hours of exposure to a contrast medium.The results of this study showed that NAC has a protective effect against RCIN even in patients with a high risk of renal dysfunction,including those with diabetes or hypertension as well as those in whom high osmolarity contrast media are used.

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The morphine equivalent of a commercially available fentanyl patch preparation (2.5 mg) is 45 to 134 mg/day (p.o.).However,for lower doses,the adhesive surface of the patch is usually covered with a semi-blocked dressing (Tegaderm^® ) to control the dose.In the present study,both in vitro and in vivo experiments were carried out to examine the drug release characteristics from such patches.
In vitro ,the drug release characteristics of a fentanyl patch (2.5 mg) with its entire surface covered with Tegaderm^® and those of a cover-free patch were compared in simulated sweat (pH 4.5),according to the dissolution test method for transdermal systems specified in the U.S.Pharmacopoeia (USP 28,paddle over disk method).Comparing the fentanyl content of the samples by HPLC showed that there was no significant difference in the percentages of drug released from either patch.
In the in vivo experiment,patches were attached to the shaved backs of rabbits (n=3)and blood samples were sequentially collected for 72 hours.Measuring the fentanyl content of serum samples by HPLC/ESI-MS showed that though the drug absorption rate was significantly reduced for the patch covered with Tegaderm^® ,the serum concentration was still at a high level after 72 hours.Also,AUC 0-72 h for the patch covered with Tegaderm^® was more than 50% of the free patch suggesting that fentanyl was released through the Tegaderm^® covering.When the entire surface of the fentanyl patch was covered with Saran wrap^® instead of Tegaderm^® ,no appreciable permeation of the drug was observed and when half of the patch surface was covered with Saran wrap ,the AUC value was around half that of the wrap-free patch.Saran wrap^® is therefore potentially useful as an auxiliary material for dose control.

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The purpose of this study was to evaluate the suspension and dispersion capabilities and bitterness intensity of seven types of antibacterial formulations on the market (azithromycin fine granules,clarithromycin dry syrup,cefditoren pivoxil fine granules,cefdinir fine granules,cefcapene pivoxil fine granules,erythromycin dry syrup,oseltamivir dry syrup) which influence palatability for pediatric patients.The particle size of the formulations was also examined since it could influence their precipitation from suspensions.At the same time we tested mixtures of oseltamivir dry syrup and four types of antibiotic formulation (2 types of macrolide antibiotic formulation : azithromycin fine granules and clarithromycin dry syrup ; 2 types of cephem antibiotic formulation : cefditoren pivoxil fine granules and cefcapene pivoxil fine granules) assuming that these antibiotic formulations were taken with oseltamivir dry syrup.
Some formulations showed low suspension and dispersion capability and others high bitterness intensities.Further,our findings suggested that taking oseltamivir dry syrup together with macrolide antibiotic formulations markedly enhanced bitterness intensity.We concluded that pharmacists should develop formulations in consideration of palatability and should provide appropriate information on them.

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We investigated the therapeutic effect of poly (lactic-co-glycolic) acid (PLGA) nanospheres containing aclarubicin on hepatic metastases in rats following injection of the nanospheres via the portal vein.The aclarubicin-containing PLGA nanospheres were prepared by a solvent evaporation method.The PLGA nanospheres so obtained had a drug trapping efficiency of 18.4% and their mean particle size was 761 nm.The release profiles of aclarubicin from the PLGA nanospheres showed that 33.9% of the drug was released from the nanospheres on the first day and another 65.0% of the drug was gradually released over the following 7 days.After the intravenous administration of the PLGA nanospheres to the rats,the aclarubicin concentrations in the liver and spleen were significantly higher than those due to injection of aclarubicin solution,while the aclarubicin concentrations in the lungs and thymus were significantly lower.On evaluating the antitumor effect of the aclarubicin in the PLGA nanospheres on the hepatic metastases in the rats,the survival time was significantly longer than for rats treated with aclarubicin solution.A histological examination showed necrosis in the metastatic lesions only in the group treated with the PLGA nanospheres.These findings suggested that aclarubicin-containing PLGA nanospheres could be a more effective formulation for treating hepatic metastases.

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In Fukuoka University Hospital,the Clinical Research Assist Center and Department of Pharmacy provide support for clinical studies with a view to ensuring the ethical soundness,reliability,and scientific precision of investigator-initiated clinical research as well as commercially-based clinical trials.For an investigator-initiated comparative clinical study conducted according to a randomized,placebo-controlled design using the double dummy method,pharmacists from the Dept.of Pharmacy prepared the placebo and packaged it and commercially available medicines in blister package sheets.The Institutional Review Board of Fukuoka University Hospital approved this study based on the assumption that the preparation of the investigational agents fulfilled the quality control guidelines of Good Manufacturing Practice.In conclusion,we were able to contribute to improving the quality of translational research through the preparation of investigational agents.

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The clinical pathway (CP) is a standardized protocol used by health care professionals in charge of treatment for a specific patient population.The CP is an effective means of avoiding medical errors especially those due to chemotherapy.At Kanazawa Medical University Hospital,all patients with B-cell lymphoma are treated according to a CP including R-CHOP chemotherapy.Supportive therapies have not yet been included in the CP so the selection of medicines,their initiation and withdrawal are determined empirically by each doctor.
In the present study,we investigated prescriptions for drugs used in supportive therapies and evaluated their effectiveness in 50 patients treated according to the CP for R-CHOP chemotherapy from January 2003 to June 2006,to determine the possibility of including the supportive therapies in the CP.We found some that some supportive therapies were useful and others needed improvement.Our findings suggest that further discussion of standard supportive therapies among doctors,pharmacists,nurses and other health care professionals is required and that they should be gradually incorporated into the CP in the near future.

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Antibiotic-resistant lactic acid bacteria (RLAB) and clostridium butyricum (CB) preparations are often used to improve symptoms resulting from antibiotic-induced changes in intestinal flora.However,though the resistance of these preparations to fluoroquinolones (FQs) has not been sufficiently studied,they are sometimes prescribed in combination with FQs under off-label use.The reason for this is thought to be that all RLAB and CB preparations are considered to be resistant to all antibiotic agents.
In this study,we determined the minimal inhibitory concentrations of FQs with respect to strains isolated from five RLAB and one CB preparation using the microdilution method.Furthermore,the susceptibility to FQs of the strains isolated from the RLAB preparations was compared with that of strains isolated from conventional lactic acid preparations.The strains from most of the RLAB preparations and that from the CB preparation were found to be susceptible to FQs.There was also no difference in bacterial resistance between the RLAB and conventional lactic acid preparations.The concurrent use of RLAB and FQs under off-label use should therefore be avoided.

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We conducted a questionnaire survey to evaluate the success of the Early Exposure programme which was introduced for first-year students following the new 6-year pharmaceutical education syllabus.Under the programme,pharmacy students visited community and hospital pharmacies to experience the work of pharmacists or to listen to lectures given by them.The questionnaire was completed by the 85 community pharmacies and 39 hospital pharmacies that accepted first-year students from Kobe Pharmaceutical University,Kobe-gakuin University,or Mukogawa Women’s University in Hyogo Prefecture.
Ninety percent of the community and hospital pharmacies had provided students with the opportunity to observe their day-to-day work,60% had provided lectures and 30% had given them the chance to experience the work of the pharmacy.The pharmacists involved considered communication with students to be the most important aspect of the programme.
Though the Early Exposure programme resulted in additional work for pharmacy staff,they considered it to be worthwhile and felt that they had good communication with the students.They considered the“ethics of prescribing”,“the pharmacist as a medical specialist”,“responsibilities of pharmacists”and“the job of the pharmacist”to be the key aspects of the Early Exposure programme.However,they requested that the universities and the students think more about the significance of the programme and its objectives beforehand.Also,while they felt that the students needed to be taught how to behave more professionally,overall,they had a positive opinion of the Early Exposure programme.
Such collaboration between community and hospital pharmacies and university staff is extremely useful in the development and implementation of educational programmes for pharmacists.

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We carried out a pharmacogenetic analysis on uridine diphosphate glucuronosyltransferase (UGT)1A1 polymorphism and a pharmacokinetic analysis on irinotecan (CPT-11)and its metabolites for a patient who developed severe neutropenia after the first course of a CPT-11 (100 mg/m²),5-fluorouracil (5-FU) and leucovorin regimen (IFL regimen).Genotyping showed the patient to be homozygous for the UGT1A1*28 allele and heterozygous for UGT1A1*27 allele.In the pharmacokinetic analysis,the serum concentrations of CPT-11,SN-38,SN-38 glucuronide and 5-FU were measured.
The AUC_0-23.25h of SN-38 was 523.6 ng·h/mL at a dose of 32.5 mg/m² of CPT-11,which was higher than that in the literature at a dose of 100 mg/m².The serum concentration of 5-FU,however,was lower than that in the literature for the same dose.Lowering the dose of CPT-11 from 100 to 26 mg/m² resulted in a decrease in CEA and CA 19-9 concentrations and a reduction in the lung metastatic focus.Considered together with the change in absolute neutrophil count observed,these findings suggested that the doses of CPT-11,5-FU and L-leucovorin be adjusted to 26 mg/m²,324 mg/m² and 195 mg/m² respectively and the washout period be extended.
In conclusion,the UGT1A1 genetic analysis and follow-up monitoring of serum CPT-11 levels that we conducted facilitated the creation of a personalized IFL regimen for the patient,which improved efficacy and safety.

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Epirubicin-cyclophosphamide (EC) and fluorouracil-epirubicin-cyclophosphamide (FEC),2 epirubicin-based regimens,are often switched to docetaxel (DOC) in chemotherapy before and after breast surgery.As nail discoloration had been frequently observed during these breast cancer chemotherapy regimens,we investigated adverse drug events in nails.Drug adverse events were observed in the nails of 87% of patients treated with EC,in 83% treated with FEC,and 58% treated with DOC following the switch from EC or FEC.With regard to the time of onset,most nail discoloration appeared after second or third course of chemotherapy with EC or FEC.Adverse drug events differed depending on the chemotherapy regimen.Nail discoloration was nearly all specific to EC and FEC and nail bed pain,onycholysis,and koilonychias tended to occur with DOC.Though most adverse drug events in the nails were mild,any of Grade 2 (CTCAE v 3.0) occurring would have impaired quality of life and caused psychological stress.Therefore,pharmacists should inform patients receiving these chemotherapies of the possibility of adverse drug events in the nails and observe them carefully.They should also recommend consultation with a dermatologist as early as possible if Grade 2 adverse drug events should occur.

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