医療薬学
Online ISSN : 1882-1499
Print ISSN : 1346-342X
ISSN-L : 1346-342X
34 巻 , 3 号
選択された号の論文の12件中1~12を表示しています
総説
  • 大谷 壽一
    2008 年 34 巻 3 号 p. 223-234
    発行日: 2008年
    公開日: 2009/09/04
    ジャーナル フリー
    The pharmacokinetic and pharmacodynamic (PK/PD) approaches are essential for applying the large amount of knowledge that has been gained from recent pharmaceutical research in planning dosage regimens for individual patients in the clinical setting.However,processes for the application of such knowledge using these approaches have not yet been established and this has become a bottleneck in promoting personalized pharmacotherapy.
    The aim of this study was to establish the fundamentals for a pharmacokinetics/pharmacodynamics-based computer-aided system for planning personalized dosage regimens.We first retrospectively applied PK/PD models based on receptor occupancy theory to 2 clinical cases to demonstrate the usefulness of this theory in preventing adverse drug reactions and dealing with any that occurred.Next,we developed PK models to explain time-dependent drug interactions,for instance reduced absorption of new-quinolones due to metal cations and decreased blood levels of cyclosporine due to induction of detoxifying proteins by St.John’s Wort.
    In the personalization of dosage regimens for patients with renal dysfunction,we developed a procedure for obtaining a parameter for the contribution of renal excretion from the literature as well as a model to explain the pharmacokinetics of a combination containing a renally-excreted metabolic inhibitor.We also developed a procedure for standardizing information on pharmaceutical formulations in order to construct databases.
    In conclusion,the present study provided procedures for use with computer-aided systems in estimating the time-profiles of concentrations,effects and adverse reactions of drugs based on their individual parameters and patient data,such as dosage regimen and physiological functions,as well as the fundamentals of computer-aided systems for planning personalized dosage regimens.All of this should help in achieving personalized pharmacotherapy.
一般論文
  • 加藤 一哉, 近藤 誠一, 一色 恭徳, 片山 怜, 舟越 亮寛, 前野 拓也, 福田 太仁夫, 夏目 秀視
    2008 年 34 巻 3 号 p. 235-239
    発行日: 2008年
    公開日: 2009/09/04
    ジャーナル フリー
    We investigated the numbers of live bacteria in the lactic acid bacteria containing powder products Lac-B® granular powder (Bifidobacterium ),Lebenin® (Antibiotics-resistant lactic acid bacteria),and Biolactis® powder (Lactobacillus casei ) before and after applying the pressure-heat sealing used in making discrete preparations of these products.The numbers of live lactic bacteria in all preparations were significantly reduced by pressure-heat sealing with a drop to 1/4 of that stated in the package insert for Lac-B® granular powder.In the case of Lebenin® and Biolactis® powder,the bacteria numbers dropped to 1/10 and 1/70 of those stated,respectively.It is thus unlikely that the number of live bacteria stated in the package inserts would be achieved for these products and one could not expect the clinical effects of the bacteria to be fully manifested when discrete preparations of the latter two products were orally administered.
    In order to clarify whether the numbers of live lactic acid bacteria were reduced by heat-treatment during the sealing of the package,all products were maintained at 115°C for 5 seconds in a thermostat.The results were almost identical to those obtained for pressure-heat sealing,suggesting that the decreases in numbers of the live bacteria in discrete preparations was mainly due to the heat-treatment involved in pressure-heat sealing.
    In conclusion,we propose that when making discrete preparations of lactic acid bacteria products,in particular Lebenin® and Biolactis® powder,no heating should be used in the sealing process.
  • 進 真里華, 渡邊 真知子, 柳 真志帆, 齋藤 百枝美, 西澤 悟, 兒野 喜穂, 平林 慎一, 松田 重三, 山岡 桂子, 井上 圭三
    2008 年 34 巻 3 号 p. 240-245
    発行日: 2008年
    公開日: 2009/09/04
    ジャーナル フリー
    We investigated the preparation of a new spray containing the humectant sodium hyaluronate (HA) to alleviate dry mouth symptoms.First,twelve healthy adult subjects graded the oral retention of 4 sodium alginate (ALG) solutions with different concentrations (0.4%,0.6%,0.8% and 1.0%).They also evaluated their taste,smell,degree of irritation and texture.Next,7 healthy subjects compared the bitterness of the 1.0% ALG solution to which 0.3% or 0.6% BMI-40 had been added as a bitterness masking agent.A flavoring agent,0.08% lemon essence or 0.054% menthol,was then added to the 0.3% BMI40 and 1.0% ALG mixture and 8 healthy subjects graded the taste,smell,degree of irritation and texture of these solutions.As a result,0.08% lemon essence was selected as the flavoring agent.Finally,we compared the viscosity of our spray with commercially available spray products to determine the optimal viscosity for clinical use.
    The 1.0% ALG solution was ranked top for oral retention (p<0.0citation=1)and solutions became more bitter as the concentration of ALG increased.Bitterness tended to be masked by 0.3% BMI-40.The addition of HA at 0.1%,produced no remarkable difference in the scores for taste,smell,irritation and texture.The commercially available sprays had very high (52.9×104cP) or low (1.43~3.30 cP) viscosities and that of our new spray was medium in degree (519.5 cP).
    The results of our study suggest that the new spray we prepared is appropriate as regards taste,texture and viscosity and we now plan to evaluate its clinical use.
  • 進 真里華, 渡邊 真知子, 柳 真志帆, 齋藤 百枝美, 西澤 悟, 兒野 喜穂, 平林 慎一, 松田 重三, 山岡 桂子, 井上 圭三
    2008 年 34 巻 3 号 p. 246-251
    発行日: 2008年
    公開日: 2009/09/04
    ジャーナル フリー
    The use of a new spray designed to alleviate xerostomia symptoms was evaluated in the clinical setting.Two kinds of spray were compared,one of them containing 0.1% sodium hyaluronate (HA) and the other no HA.The other ingredients of the 2 sprays were 0.1% sodium alginate (ALG),0.3% of a commercial bitter-masking powder made from lecithin (Benecoat BMI-40)and 0.08% lemon essence.Both sprays were stored under various conditions for various periods,and the microbial enumeration test was conducted for some storage conditions.We also prepared a questionnaire for patients based on the literature and consultation with a dentist to score their xerostomia symptoms.
    The taste,smell,degree of irritation and texture of the 2 sprays were evaluated by 21 oral surgery outpatients complaining of xerostomia.Eighteen of the 21 patients completed the questionnaire before and after using one of the sprays for 7 days.The storage conditions were set at 14 days at room temperature or in a refrigerator.The questionnaire consisted of 15 items relating to xerostomia symtoms,5 to ADL and 2 items to QOL.There was an improvement in the xerostomia symptomrelated item of“drink water frequently,carry water around”for both patients using the 0.1% HA spray and the one not containing HA.This was attributed to the effect of ALG on mucous membranes.On examining total scores by underlying disease,improvement was noted for patients with xerostomia as a complication of oral ulcer,glossitis,glossodynia or lichen planus.The 2 sprays may therefore be effective in alleviating symptoms of xerostomia.
ノート
  • 西田 愛子, 三宅 健文, 辻本 雅之, 今田 直樹, 青木 正, 高良 恒史, 横山 照由
    2008 年 34 巻 3 号 p. 252-255
    発行日: 2008年
    公開日: 2009/09/04
    ジャーナル フリー
    A 60-year-old male was diagnosed with a polycystic kidney disease,and maintenance hemodialysis was initiated on an outpatient basis in February 2002.In February 2004,he was started on 0.125 mg/day of digoxin three times a week after hemodialysis.Later,60 mg of fexofenadine twice daily was co-administered with the digoxin during 2 periods : August 7 to September 28,2004 (Period A) and April 13 to December 20,2005 (Period B).
    The trough concentration of digoxin tended to be lower in Period A,and the trough concentration of digoxin,which was 1.0 ng/mL just before Period B,decreased gradually to a level less than the limit of detection (0.3 ng/mL) in around 4 months.This decrease was maintained for at least 3 months after discontinuing the administration of fexofenadine.Blood samples were collected before hemodialysis,and the serum concentration of digoxin was measured once a month by enzyme immunoassay.Drugs known to decrease serum digoxin concentrations were not administered during the surveillance period.
    In conclusion,our findings suggest that the co-administration of fexofenadine with digoxin could decrease the serum concentration of digoxin in patients undergoing hemodialysis.
  • 永田 将司, 日高 宗明, 大野 梨絵, 岩切 智美, 奥村 学, 有森 和彦, 鈴木 彰人, 河内 明夫, 徳永 仁, 平井 正巳, 高村 ...
    2008 年 34 巻 3 号 p. 256-262
    発行日: 2008年
    公開日: 2009/09/04
    ジャーナル フリー
    The Japanese Society of Hospital Pharmacists has proposed the“Group Hospital Internship Program”to enrich the practical training of pharmacy students.Under this program,1 principal hospital (core hospital in an area) and 2 or more other hospitals form a group to conduct tasks that would be impossible for each hospital to carry out individually.However,as this was expected to increase the workload of pharmacists at the principal hospital,faculties of pharmacy schools were dispatched to the pharmacy of the principal hospital in order to ensure that the group hospital internship went smoothly.
    Doing this enabled the group hospital internship to be conducted without increasing the workload of pharmacists at the principal hospital,and most of the pharmacy students thought the practical training they received in the principal hospital’s pharmacy was necessary.Our findings suggest that it is useful for pharmacy students and hospital pharmacists to participate in a group hospital internship conducted by the faculties of pharmacy schools.
  • 嶽本 絵理, 岡田 祥恵, 向井 淳治, 石坂 敏彦, 内田 享弘
    2008 年 34 巻 3 号 p. 263-267
    発行日: 2008年
    公開日: 2009/09/04
    ジャーナル フリー
    The purpose of the present study was to evaluate several factors affecting the palatability of 7 kinds of antibacterial formulation (azithromycin fine granules,clarithromycin dry syrup,cefditoren pivoxil fine granules,cefdinir fine granules,cefcapene pivoxil fine granules,erythromycin dry syrup,oseltamivir dry syrup) for pediatric use by the SD (Semantic Differential) method.
    There were 15 evaluation items altogether,consisting of 10 items obtained from gustatory sensation testing and 5 obtained from package inserts.Based on a principal ingredient analysis,items having a high factor loading were“palatability”,“particle persistence in mouth”,“feeling to tongue”,“tendency to cause diarrhea”,“bitterness (as suspension for 10 mins),“smell (as powder)”,“ease of suspension”,“drug-food/beverage interaction”and“familiarity of taste”.The SD method proved useful in deriving factors affecting palatability,and using the high factor loading item scores,we were able to created overall palatability profiles graphically for the 7 types of antibacterial formulation for comparison purposes.
  • 三宅 知宏, 橋田 亨, 小林 政彦, 寺田 智祐, 桂 敏也, 安田 浩康, 三尾 直士, 柳原 一広, 福島 雅典, 乾 賢一
    2008 年 34 巻 3 号 p. 268-273
    発行日: 2008年
    公開日: 2009/09/04
    ジャーナル フリー
    Amrubicin hydrochloride (AMR) is usually administered intravenously to lung cancer patients at 45 mg/m2 for 3 consecutive days every 3 or 4 weeks.As such chemotherapy is used for patients who have already received other chemotherapies,the recommended dosage in the package insert is usually reduced.In the present study,the clinical usage and adverse drug reactions of AMR were investigated in outpatients with lung cancer treated with the drug at the Outpatient Oncology Unit of Kyoto University Hospital between October 2005 and September 2006.Patient profiles,previously performed regimens and initial dosages of AMR were examined,and hematological toxicities were compared with those reported in clinical trials.
    Seventeen outpatients (44-79 years) had been treated with AMR.All of them had received other chemotherapies with the number of previous chemotherapies ranging from 2-7.The average dose of AMR in the first administration was 35.4±5.5 mg/m2,lower than the recommended dose of 45 mg/m2.Neutropenia (Grade 3 or 4)and thrombocytopenia occurred in 47.1 % and 5.9% of the patients,respectively,these frequencies being lower than those reported in clinical trials.Patients experiencing hematological toxicity had neutrophil counts of less than 3,500/μL before chemotherapy.In view of our findings,pharmacists should pay attention to therapeutic histories and hematological profiles in order to perform AMR therapy more safely and effectively.
  • 石塚 洋一, 近藤 悠希, 山川 枝里子, 薬師神 壮, 前田 記代子, 辻口 憲司, 丸山 徹, 森内 宏志, 入倉 充, 入江 徹美
    2008 年 34 巻 3 号 p. 274-280
    発行日: 2008年
    公開日: 2009/09/04
    ジャーナル フリー
    As ambiguous package descriptions occasionally cause medication errors,measures against this should be taken to help ensure that medicines are used properly.An example is Speel plaster® M,a salicylic acid adhesive plaster,which is used for the treatment of dermal diseases with keratosis.It is supposed to be attached to the diseased skin in a size the same as that of the affected area or smaller than it,in order to prevent the normal skin surrounding the affected area from being irritated and/or being detached.However,we found that some patients covered an area larger than the affected area with the plaster.This may be due to misunderstanding of a Japanese expression in the package description.The expression is “Kanbu-dai”which means the same size as the affected area but some patients take“dai”to mean large making them think that the size should be larger.
    In a questionnaire given to 180 pharmacy school students,65.6% answered that the proper use of the plaster was to apply it in a size larger than the affected area,since they had misunderstood the meaning of the expression“Kanbu-dai”.This misunderstanding seemed to be connected with the fact that they had not used the plaster before.We therefore devised a user-friendly package with an explanation to patients using illustrations to help ensure that the plaster is used properly.
  • 栗原 祐子, 小野田 資, 竹澤 正明, 土肥口 泰生, 上杉 恵三
    2008 年 34 巻 3 号 p. 281-288
    発行日: 2008年
    公開日: 2009/09/04
    ジャーナル フリー
    Warfarin is the only oral anticoagulant used in the prevention of thromboembolism in Japan.The anticoagulant effect of warfarin is monitored by analysis of the prothrombin complex (International Normalised Ratio,INR),but in some cases,measurement of plasma warfarin concentrations is necessary.
    We developed simple and sensitive LC/MS/MS methods for this purpose and validated it through assay of four warfarin monohydroxylated metabolites and warfarin enantiomers in human plasma.Preparation of samples from 0.05 mL of plasma involved simple protein precipitation using hydrochloric acid/acetonitrile.Analytes remained stable during sample processing and storage.Chromatographic separation was conducted using a chiral (CHIROBIOTIC V) column and an achiral (Symmetry Shield RP18)column.No significant interference from human plasma components was observed.Assay linearity was demonstrated for all analytes with the LC/MS/MS system over the calibration range 2 to 500 ng/mL.The intra-day and inter-day assay precisions expressed as coefficients of variation (C.V.) for the quality control samples (4,40 and 400 ng/mL) were not more than 9.0%.In conclusion,this system was considered to be reliable enough for the evaluation of pharmacokinetic profiles in planned clinical studies.
  • 名取 伸行, 花輪 和己, 鈴木 正彦, 花輪 剛久, 小口 敏夫
    2008 年 34 巻 3 号 p. 289-296
    発行日: 2008年
    公開日: 2009/09/04
    ジャーナル フリー
    A questionnaire survey of inpatients of widely varying ages was conducted to investigate the ease of taking internal medicines and desired dosage forms.A similar questionnaire survey of nurses and pharmacists working in a university hospital was also conducted to compare awareness of dosage forms by profession.The results of this survey clearly demonstrated the difference in awareness of patient preference regarding internal medicines among pediatric nurses,nurses working at other hospital wards,and pharmacists.This discrepancy seemed to reflect the difference in awareness of different health care workers concerning impairment of deglutition capability with aging.Awareness of patients' desired dosage forms also varied between pharmacists and nurses,which could be due to the difference in knowledge of pharmaceutics between these 2 professions.Based on the results of this study,it was felt that pharmacists should provide medication instruction to individual patients and provide pharmaceutical information to nurses,and that information sharing is important to ensuring that proper pharmaceutical care is conducted in the hospital.
  • 板垣 文雄, 菅 真悠子, 本間 真人, 長谷川 雄一, 小島 寛, 神林 泰行, 幸田 幸直
    2008 年 34 巻 3 号 p. 297-301
    発行日: 2008年
    公開日: 2009/09/04
    ジャーナル フリー
    Anthracycline (AC) induced cardiotoxicity is a dose limiting factor in anti-cancer chemotherapy including AC.It has been reported that AC induced cardiotoxicity increases when the cumulative dose exceeds 500 mg/m2 (calculated as doxorubicin).In view of this,we investigated accumulation rates in 59 patients with hematological malignancies,and estimated the time taken for it to reach 500 mg/m2 for the 3 major regimens of high-CHOP,CHOP and VAD,to Compare the differences between predicted values calculated from the initial dose of AC for each regimen.The relationship between the cumulative dose of AC and cardiotoxicity for several chemotherapies including AC was also investigated.The accumulation rate of AC was 1.37 (0.17-3.14)mg/m2/day and the cumulative dose of 500 mg/m2 would be reached 170,231 and 495 days after starting high-CHOP,CHOP and VAD,respectively,which was 10-27% longer than the times predicted on the basis of the initial dose of AC for each regimen.A positive correlation was found between electrocardiographic QTc and cumulative dose of AC (r=0.448,p<0.05).As two of five patients in whom the cumulative dose reached 500 mg/m2 of AC developed cardiomyopathy,AC cardiotoxicity should be intensively monitored 170-495 days after starting the chemotherapies such as high-CHOP,CHOP and VAD,when the cumulative dose is approaching 500 mg/m2.
feedback
Top