YAKUGAKU ZASSHI
Online ISSN : 1347-5231
Print ISSN : 0031-6903
ISSN-L : 0031-6903
131 巻, 4 号
選択された号の論文の23件中1~23を表示しています
誌上シンポジウム
  • 合田 光寛, 山本 由似
    2011 年 131 巻 4 号 p. 485
    発行日: 2011年
    公開日: 2011/04/01
    ジャーナル フリー
  • 名和 文花, 藤田(濱邊) 和歌子, 中本 賀寿夫, 徳山 尚吾
    2011 年 131 巻 4 号 p. 487-492
    発行日: 2011/04/01
    公開日: 2011/04/01
    ジャーナル フリー
      P-glycoprotein (P-gp), one of the important drug-efflux pumps, is known to be affected by pathological conditions such as inflammation or infection. Recently, it is reported that high glucose or hyperglycemia can alter P-gp expression levels at the blood-brain barrier or in kidney, although the details are still unknown. Here, we analyzed the alteration of intestinal P-gp expression and function in the development of diabetes and elucidated the mechanisms. Type 1 diabetes was induced in male ddY mice by an i.p. injection of streptozotocin (STZ) (230 mg/kg). We analyzed ileal P-gp expression and drug efflux activity using western blot analysis and an in situ closed loop method, respectively. Additionally, we analyzed ileal nitric oxide synthase (NOS) activity using colorimetric method. A significant reduction of P-gp expression level in ileum was found on day 9 after STZ administration. In contrast, a remarkable decrease in drug efflux activity was observed on days 3 and 9. Interestingly, NOS activity in ilea was significantly increased on day 9. The decrease of P-gp expression levels observed on day 9 was completely suppressed by L-NG-nitroarginine methyl ester (L-NAME), a broad range NOS inhibitor, or aminoguanidine, a specific inducible NOS (iNOS) inhibitor. In addition, P-gp expression level in ileum was significantly decreased by administration of NOR5, a NO donor. These results indicate the possibility that NO, produced by iNOS in the ileum, is involved in the alteration of ileal P-gp expression and function under STZ-induced diabetic conditions.
  • 岩切 詩子, 仙波 純一, 末永 啓二, 島添 隆雄
    2011 年 131 巻 4 号 p. 493-496
    発行日: 2011/04/01
    公開日: 2011/04/01
    ジャーナル フリー
      The mortality risk of metabolic disease for psychotic patients is reported to be high. Therefore, in this research, we investigated the compliance with drug therapy among psychotic patients who had diabetes or dyslipidemia. Based on this investigation, we counseled and educated the patients from the pharmaceutical point of view. The effects of pharmaceutical consultation and education were evaluated based on the compliance rate of drug therapy, body mass index (BMI), and blood glucose and cholesterol levels. A significant difference was found between the drug therapy compliance rate and blood glucose level after consultation and education. However, there was no significant difference in the BMI and blood cholesterol level. Our results suggest that patient education is effective in increasing the drug therapy compliance rate and reducing blood glucose levels in psychotic patients.
  • 山本 由似, 塩田 倫史, 大和田 祐二, 福永 浩司
    2011 年 131 巻 4 号 p. 497-501
    発行日: 2011/04/01
    公開日: 2011/04/01
    ジャーナル フリー
      Haloperidol as a potent dopamine D2 receptor (D2R) antagonist was a major tranquilizer to treat schizophrenia patients. However, the D2R blocking action in dorsal striatum is thought to cause extrapyramidal symptoms as adverse effects. However, the pathophysiological mechanism underlying extrapramidal symptoms induced by chronic treatment of haloperidol remains unclear. We recently found that lacking of heart-type fatty acid binding protein (H-FABP) in the brain aggravate catalepsy behavior induced by haloperidol. Here, we examined neuronal mechanism of augmentation of haloperidol-induced catalepsy in H-FABP null mice. Notably, catalepsy induced by haloperidol, a D2 antagonist, is augmented, whereas catalepsy induced by SCH23390, a D1 antagonist, was not affected in H-FABP null mice. Interestingly, haloperidol-induced acetylcholine (ACh) release in the dorsal striatum was markedly enhanced in H-FABP null mice compared to wild mice. We also defined the co-localization of D2R with H-FABP in the ACh interneurons in the striatum. Taken together, H-FABP regulates dopaminergic neuronal activity through interaction with D2R in rodent brain. The increased ACh release in the striatum accounts for haloperidol-induced catalepsy.
  • 徳山 尚吾, 福永 浩司
    2011 年 131 巻 4 号 p. 503-504
    発行日: 2011年
    公開日: 2011/04/01
    ジャーナル フリー
  • 塩田 倫史, 山本 由似, 韓 峰, 森口 茂樹, 福永 浩司
    2011 年 131 巻 4 号 p. 505-511
    発行日: 2011/04/01
    公開日: 2011/04/01
    ジャーナル フリー
      Loss of cholinergic neurons and/or dysfunction of the glutamatergic system in the central nervous system cause learning impairment in experimental Alzheimer's (Alz) disease animals and Alz patients. Furthermore, the impaired cholinergic system is likely implicated in depressive behaviors in Alz patients. Neurogenesis persistently occurs in the forebrain subventricular zone (SVZ) and hippocampal subgranular zone (SGZ) in rodent and human brains. Notably, impaired neurogenesis in those regions is implicated not only in memory deficits but also in depressive behaviors. We have recently found that olfactory bulbectomized (OBX) mice reveal memory impairment and depressive behaviors. Using this attractive OBX mice model, we discovered a novel cognitive enhancer, spiro[imidazo[1,2-a]pyridine-3,2-indan]-2(3H)-one (ZSET1446/ST101), that is a new azaindolizinone derivative without inhibitory action on acetylcholine esterase (AChE). Interestingly, ZSET1446 improved learning and memory by potentiating nicotine-induced ACh release in the hippocampus of amyloid-beta infused rats. In addition, ZSET1446 restored OBX-induced cognitive deficits in mice. Furthermore, chronic ZSET1446 administration significantly rescues decreased neuronal precursor cell proliferation seen in the dentate gyrus of OBX mice. Consistent with enhanced neurogenesis, chronic ZSET1446 administration improved depressive behavior assessed using the tail suspension test in OBX mice. Protein kinase B (Akt) and extracellular signal-regulated kinase pathways likely mediate ZSET1446-induced neurogenesis. These results suggest that ZSET1446 action via stimulation of the cholinergic system elicits improvement of the depression and cognitive impairment observed in Alz disease patients.
  • 石黒 光紀, 原 英彰
    2011 年 131 巻 4 号 p. 513-521
    発行日: 2011/04/01
    公開日: 2011/04/01
    ジャーナル フリー
      Cilostazol, a selective inhibitor of phosphodiesterase III, is an antiplatelet drug and a vasodilator via increased cAMP levels. It has been approved for the treatment of ischemic symptoms in chronic peripheral arterial obstruction or intermittent claudication and for secondary prevention of cerebral infarction (CSPS I). Recently, cilostazol has been reported to be more effective than aspirin in the secondary prevention of all types of stroke in patients and, in particular, prevent the secondary attack of hemorrhagic stroke in patients (CSPS II). Laboratory investigations revealed that cilostazol has a neuroprotective effect against ischemic brain injury. The neuroprotective potential is dependent on its antiinflammatory and antiapoptotic effects mediated by scavenging hydroxyl radicals, decreasing formation of tumor necrosis factor-α, and inhibition of poly (ADP-ribose) polymerase activity. In addition, increasing evidence indicates that cilostazol may offer endothelial protection via both the inhibition of lipopolysaccharide-induced apoptosis and induced nitric oxide (NO) production by endothelial NO synthase activation. The breakdown of the barrier permeability of the blood brain barrier (BBB) often accelerates the progression of diseases such as cerebral ischemia. However, the molecular mechanisms involved in BBB disruption have not been fully determined. Identification of the molecules responsible for the disruption of the endothelial barrier may yield new therapeutic targets in intractable diseases. This article reviews the protective effects of cilostazol against transient focal cerebral ischemia and hemorrhagic transformation and its mechanism of action.
  • 山本 巌, 副田 二三夫, 白﨑 哲哉, 高濱 和夫
    2011 年 131 巻 4 号 p. 523-532
    発行日: 2011/04/01
    公開日: 2011/04/01
    ジャーナル フリー
      Clinically, both overactive bladder (OAB) and dysuria are known to occur in patients with cerebral infarction (CI). A few anticholinergic drugs are used to treat OAB in such patients, although the effect is not satisfactory. On the other hand, little or no therapeutic drug is available for dysuria after CI. We previously reported that dextromethorphan (DM) and cloperastine (CP), centrally acting antitussives, reduce the frequency of micturition reflex and increase the threshold pressure in anesthetized rats. In this article, we describe the effects of DM and CP on urinary disturbances at 24 h after CI, induced by occlusion of the left middle cerebral artery in conscious rats. We also briefly review the structure, function, and distribution of G-protein-coupled inwardly rectifying K+ (GIRK) channels in the brain, since both drugs have potent inhibitory effect on GIRK channel-activated currents in brain neurons. Of the two drugs, CP at antitussive-effective doses ameliorated both OAB and dysuria 24 h after CI in rats. On the other hand, DM aggravated the dysuria, although it significantly ameliorated the OAB. These results suggest that CP may have some therapeutic value for the treatment of OAB and dysuria after CI. At the present time, mechanisms of the effect of CP are unknown. However, several lines of evidence including pharmacological findings support the idea that the effects of CP may be produced at least partly by an increase in the level of 5-HT in the brain through an inhibitory effect on GIRK channel-activating currents.
  • 藤田(濱邊) 和歌子, 原田 慎一, 徳山 尚吾
    2011 年 131 巻 4 号 p. 533-538
    発行日: 2011/04/01
    公開日: 2011/04/01
    ジャーナル フリー
      Hyperglycemia is a known exacerbating factor in ischemic stroke. It has been reported that hyperglycemia and post-ischemic glucose intolerance can develop after stroke and be involved in the development of neuronal damage, as we described previously. Here, we focus on the effectiveness of metformin, a hypoglycemic drug, in preventing the development of neuronal damage using the middle cerebral artery occlusion (MCAO) model mice. 5′-AMP-activated protein kinase (AMPK) is a serine/threonine kinase that plays a key role in the hypoglycemic effects of metformin. Recently, it has been reported that centrally activated AMPK is involved in the development of ischemic neuronal damage, while the effect of peripherally activated AMPK on ischemic neuronal damage is not known. In the liver, AMPK activity was not affected by MCAO, while the administration of intraperitoneal metformin (250 mg/kg), an AMPK activator, significantly activated hepatic AMPK and suppressed both the development of post-ischemic glucose intolerance and ischemic neuronal damage without alteration of central AMPK activity. On the other hand, the administration of intracerebroventricular metformin (100 μg/mouse) significantly exacerbated the development of neuronal damage observed on day 1 after MCAO. These effects were significantly blocked by compound C, a specific AMPK inhibitor. These results suggest that central AMPK is activated by ischemic stress per se, although peripheral AMPK is not altered. Furthermore, the regulation of post-ischemic glucose intolerance by metformin-induced activation of peripheral AMPK contributes to the reduction of cerebral ischemic neuronal damage.
  • 南 雅文
    2011 年 131 巻 4 号 p. 539-544
    発行日: 2011/04/01
    公開日: 2011/04/01
    ジャーナル フリー
      The brain contains glial cells (astrocytes, microglia, and oligodendrocytes) and endothelial cells in addition to neurons. Under various pathologic conditions, the invasion of leukocytes such as neutrophils, monocytes/macrophages, and lymphocytes is observed. Interactions among these cell types play crucial roles both in brain function and dysfunction. However, the molecular basis of such interactions remains unclear. Cytokines and chemokines were originally identified as essential mediators of inflammatory and immune responses. Enhanced production and release of cytokines/chemokines are observed also in the central nervous system under various pathologic conditions. There is growing evidence showing that brain cytokines/chemokines play crucial roles in the neuro-glio-vascular interaction underlying the pathology of various brain disorders and therefore are potential targets for the development of novel and effective therapeutics for central nervous system diseases. This article reviews the evidence for the involvement of cytokines/chemokines in ischemic brain injury and presents our data on introducing organotypic brain slice cultures and in vitro blood brain barrier models as useful tools to investigate neuro-glio-vascular interaction.
総説
  • 宮本 和範
    2011 年 131 巻 4 号 p. 545-552
    発行日: 2011/04/01
    公開日: 2011/04/01
    ジャーナル フリー
      In this review, we show that intermolecular hypervalent I(III)…O interactions play an essential role in the complexation of organo-λ3-iodanes with crown ethers. In addition to the well-known driving force for the complexation of crown ethers, ion-dipole interaction, and hydrogen bonding interaction, our result provides a new class of interaction in supramolecular chemistry of crown ethers. Both solid state structure analysis and solution chemistry indicate that diaryl-, 1-alkenyl(phenyl)-, 1-alkynyl(phenyl)-, and hydroxy(phenyl)-λ3-iodanes form stable complexes with 18-crown-6 through hypervalent I(III)…O interactions. The complexation not only increases the stability of these hypervalent λ3-iodanes but also holds its high reactivity toward nucleophiles. The complex of hydroxy(phenyl)-λ3-iodanes with 18-crown-6 serve as versatile oxidizing agents, especially in water.
  • M. M. A. MAMUN, A. K. M. N. HUDA
    原稿種別: Review
    2011 年 131 巻 4 号 p. 553-562
    発行日: 2011/04/01
    公開日: 2011/04/01
    ジャーナル フリー
      Swine influenza viruses cause annual epidemics and occasional pandemics claiming the lives of millions from the early history up to the present days. This virus has drawn on a bag of evolutionary tricks to survive in one or another form in both humans and pigs with novel gene constellations through the periodic importation or exportation of viral genes. A prime example is emergence of pandemic novel swine-origin influenza A (H1N1) virus (S-OIV) in 2009 that have transmitted to and spread among humans, resulting in outbreaks internationally. The phylogenetic analysis of sequences of all genes of the S-OIV, showed that its genome contained six gene segments that were similar to ones previously found in triple-reassortant swine influenza viruses circulating in pigs in North America. The genes encoding neuraminidase and M protein were most closely related to those in influenza A viruses circulating in swine populations in Eurasia. This unique genetic combination of influenza virus gene segments leading to the emergence of novel S-OIV that had not been seen before in the world. Here, it has been used evolutionary analysis to estimate the timescale of the origins and the early development of the S-OIV epidemic. This paper shows that it was derived from several viruses circulating in swine and makes a briefly review over the origins and evolutionary genomics of current S-OIV in humans with historical perspectives with a view to exhibition of evolutionary relationship between past and present origins of swine influenza viruses.
一般論文
  • 今浦 将治, 木幡 雄至, 小林 光太郎, 髙橋 宏行, 横山 晴子, 赤瀬 朋秀, 山田 安彦
    2011 年 131 巻 4 号 p. 563-570
    発行日: 2011/04/01
    公開日: 2011/04/01
    ジャーナル フリー
      Pharmacists are providing pharmaceutical care in general wards, but it is still not common in the intensive care unit (ICU). However, we have worked in ICU, and recommended the rational dosage regimen of the antibiotics to the physicians during the treatment period. Especially, the patients who were infected with methicillin-resistant Staphylococcus aureus (MRSA) in ICU should be provided appropriate antibiotic therapy, otherwise they have a poor prognosis. The aim of this study is to evaluate usefulness of the pharmacists' intervention on the antibiotic therapy for MRSA infectious diseases in the ICU. We investigated retrospectively the period of anti MRSA drugs administration, the medical cost, which includes cost of anti MRSA drugs and hospital charge, and the initial trough concentration of vancomycin (VCM). The patients with MRSA pneumonia were classified into two groups according to the pharmacists' intervention. The number of the patients who the pharmacists performed dosage regimen of anti MRSA drug was 11 (intervention group) and that of the patients who the pharmacists performed no intervention was 47 (control group). The average period of administration of anti MRSA drugs in the intervention group was significantly decreased in 5 days. Furthermore, if the pharmacists performed dosage regimen of anti MRSA drug to the patients in control group, the medical cost of 10 million yen would be saved. The initial trough concentrations of VCM were not significantly different between two groups. However, the achievement rates are 75.0% in intervention group and 66.7% in control group, if the goal of trough level of VCM is set from 5 to 15 μg/ml. Moreover, there are 75.0% in intervention group and 20.8% in control group, if the goal of trough level of VCM is set from 10 to 20 μg/ml, which is significantly different between the two groups. Therefore, it was suggested that the pharmacists in the ICU contributed to optimize the anti MRSA therapy and reduce the medical cost.
  • 内倉 健, 横井 伸至, 橋口 正行, 望月 眞弓
    2011 年 131 巻 4 号 p. 571-580
    発行日: 2011/04/01
    公開日: 2011/04/01
    ジャーナル フリー
      The effectiveness and safety of angiotensin-converting enzyme (ACE) inhibitors for the treatment of hypertension have been confirmed during long-term use. Therefore, ACE inhibitors were selected as one candidate for the switch from ethical drugs to over-the-counter (OTC) medications. The objective of this study was to perform a cost-effectiveness analysis if ACE inhibitors were switched to OTC medications and used by grade I hypertension patients in Japan. We conducted a cost-effectiveness analysis from a social perspective over a lifetime horizon using a Markov Model in 50-year-old men and women with grade I hypertension. They were divided into 3 groups: 1) untreated group; 2) consultation group visiting a clinic and receiving prescriptions for ACE inhibitors; and 3) OTC group purchasing OTC ACE inhibitors. The cost of OTC medications was estimated based on a previous study of willingness to pay (¥7,237/month). Average life expectancies in both the OTC and consultation groups were 20.20 for men and 22.63 for women, while in the untreated group it was 19.97 for men and 22.47 for women. Incremental costs per expected life-year (ICER) were ¥1,743,557 for men and ¥8,647,069 for women in the OTC group and ¥3,819,861 for men and ¥9,639,844 for women in the consultation group. These results suggest that longer life expectancies can be achieved with ACE inhibitors, and the total cost is decreased using OTC ACE inhibitors compared with ethical drugs. OTC ACE inhibitors therefore appear be a useful alternative for patients who do not have time to visit a clinic regularly.
  • 高野 憲一, 井野口 友紀, 倉地 道雄
    2011 年 131 巻 4 号 p. 581-586
    発行日: 2011/04/01
    公開日: 2011/04/01
    ジャーナル フリー
      Atopic dermatitis is a chronic and relapsing inflammatory skin disease that is characterized by highly pruritic, eczematous skin lesions. Our previous study elucidated that nerve growth factor (NGF) plays an important role in the pathogenesis of skin lesions and inhibition of the physiological effects of NGF can moderate skin lesions in atopic dermatitis. In this study, we investigated the effects of ethanol extracts of herbal medicines on neuritic outgrowth induced by NGF. Four herbal extracts (Geranium thunbergii, Humulus lupulus, Rosmarinus officinalis and Salvia officinalis L.) inhibited NGF-induced neuritic outgrowth in PC12 cells. We also investigated the effects of each herbal extract on dermatitis in NC/Nga, an atopic dermatitis mouse model. The skin lesions of the NC/Nga mice were significantly inhibited by repeated applications of each herbal extract. These results suggested that the four herbal extracts can prevent and moderate the symptoms of atopic dermatitis, and these effects might be appeared by inhibiting the effect of NGF on neuritic outgrowth in lesional skin.
  • 寺町 ひとみ, 駒田 奈月, 谷沢 克弥, 葛谷 有美, 土屋 照雄
    2011 年 131 巻 4 号 p. 587-595
    発行日: 2011/04/01
    公開日: 2011/04/01
    ジャーナル フリー
      To purpose of this study was to develop a pharmacist communication skill scale. A 38 items scale was made and 283 pharmacists responded. The original questionnaire consisted of 38 items, with 1-5 graded Likert scale. Completed responses of 228 pharmacists data were used for testing the reliability and the validity of this scale. The first group of items from the original questionnaire were 38, and finally 38 original items were chosen for investigation of content validity, correlation coefficient and commonality. From factor analysis, four factors were chosen among the 31 items as follows: patient respect reception skill, problem discovery and solution skill, positive approach skill, feelings processing skill. The correlation coefficient between this original scale and the KiSS-18 (Social Skill) received high score (r=0.694). The reliability of this scale showed high internal consistency (Cronbach α coefficient=0.951), so the result of test for the validity of this scale supports high content validity. Thus we propose adoption of pharmacist communication skill scale to carry a brief eponymous name as TePSS-31. The above findings indicate that this developed scale possess adequate validity and reliability for practical use.
  • 垣見 和之, 丹羽 敏幸, 檀上 和美
    2011 年 131 巻 4 号 p. 597-601
    発行日: 2011/04/01
    公開日: 2011/04/01
    ジャーナル フリー
      An eccentric-type tablet machine fitted with 8-mm-diameter flat-faced punches was used to measure the forces of upper and lower punches, die-wall pressure, tablet ejection force, and scraper pressure (SCR), a type of shear stress, to evaluate sticking behavior. The shear stress between the surfaces of the tablet and lower punch was determined using an SCR detection system. Mean surface roughness (Ra) of tablets, measured by laser scanning microscopy, was used to estimate the magnitude of sticking. Tablet tensile strength tended to increase with compression pressure, which is consistent with previous reports. SCR decreased with increasing compression pressure for samples at all formulations (i.e., for different kinds and percentages of lubricant). Ra associated with sticking increased with SCR, indicating that the adhesive force between the particles of the tablet surface and the lower punch surface plays an important role in sticking. Multiple linear regression analysis with SCR as the response variable was conducted. Upper and lower punch force, die-wall pressure, tablet ejection force, SCR, percentage of lubricant, and tensile strength of tablet were selected as explanatory variables. Results of this analysis indicate that the incidence of sticking decreased when either the lower punch force or die-wall pressure increased, where, of these two, increasing the lower punch force had a stronger effect on decreasing SCR.
  • 村松 信, 有末 友三子
    2011 年 131 巻 4 号 p. 603-619
    発行日: 2011年
    公開日: 2011/04/01
    ジャーナル フリー
      We analyzed the therapeutic target molecules and biochemical properties of 893 new drugs with new molecular entities approved over three decades from 1980 to 2009 in Japan. According to our analysis of the therapeutic targets, 26.2% of new drugs were enzymes. Membrane receptors were found to be the second-most frequent molecular targets of the new drugs, representing 25.3% of the new drugs approved. The biochemical properties of the drugs were found to have changed over time. Though the total number of new drugs approved from the year 2000 was smaller than that in the 1980s and 1990s, the number of new protein drugs approved in the 2000s, largely recombinant bioactive substances and monoclonal antibodies, increased significantly compared with those approved in the 1980s and 1990s. The results obtained in this study indicated changes in the therapeutic targets, biochemical properties and therapeutic areas of new drugs approved over the last 30 years and suggest the aspects of the future development of new drugs.
  • 長井 紀章, 村尾 卓俊, 犬伏 梨乃, 小西 菜穂子, 伊藤 吉將
    2011 年 131 巻 4 号 p. 621-628
    発行日: 2011/04/01
    公開日: 2011/04/01
    ジャーナル フリー
      Dissolution testing is a core performance test in pharmaceutical development and quality control. The conventional HPLC dissolution method (batch-sampling method) has many steps such as the filtration, collection and replenishment of sample solutions. We previously reported the dissolution test by using microdialysis methods (microdialysis-HPLC method) that can omit many steps. In this study, we investigated whether the microdialysis-HPLC method can be applied to quality assessment for sustained release preparations by a dissolution test. Calcium-channel blockers nifedipine tablets (20 mg) were used, and the test solution used was 0.2 M hydrogen phosphate-citric acid buffer (pH 6.8) with or without 1% sodium lauryl sulfate. In both test solutions, the microdialysis-HPLC method is able to accomplish continuous sampling of sample solutions, and the dissolution behaviors of original nifedipine tablets by the microdialysis-HPLC method were similar to that of the batch-sampling method. In contrast, the dissolution behaviors by the microdialysis-HPLC method were different between original nifedipine tablets and generic products, and the dissolution behaviors in the microdialysis-HPLC method tend to reflect the pharmaceutical design in comparison with the batch-sampling method. In addition, standard deviation in the microdialysis-HPLC method was lower than that of the batch-sampling method. We found that the recovery rate of nifedipine by the microdialysis-HPLC method was increased with the decrease in flow rate through dialysis probe. These findings provide significant information that can be used in pharmaceutical development and quality assessment for original and generic pharmaceutical products, which are sustained release preparations.
ノート
  • 久保 儀忠, 八木 直美, 関川 彬
    2011 年 131 巻 4 号 p. 629-634
    発行日: 2011/04/01
    公開日: 2011/04/01
    ジャーナル フリー
      After solid dispersion systems of probucol-polyvinylpyrrolidone K30 (1 : 9 in weight ratio) were exposed to light (10000 lx) for 7 days, 84% of the probucol remained. Commercial probucol fine granules were thus fairly stable under light exposure. When solid dispersion systems were stored in heat-sealed packages at relative humidity (R.H.) of 75% and 92% for 30 days at 30°C, the weight of the samples increased by 22% and 43%, respectively. When these solid dispersion systems were dissolved in water, the probucol concentration decreased with the duration of storage. The crystalline nature of probucol in the solid dispersion systems could not be detected by powder X-ray diffraction or differential scanning calorimetry. After passing the dissolution medium through the membrane filter, retention time of the residue on the filter in the HPLC method corresponded to that of probucol. These results suggest that the partial crystallization of probucol in the solid dispersion systems may occur during storage under these conditions. Solid dispersion systems in heat-sealed packages were fairly stable when stored under room conditions or in light-resistant tightly sealed containers for 5 months.
資料
  • 松原 和夫, 外山 聡, 佐藤 博, 鈴木 洋史, 粟屋 敏雄, 田崎 嘉一, 安岡 俊明, 堀内 龍也
    2011 年 131 巻 4 号 p. 635-641
    発行日: 2011/04/01
    公開日: 2011/04/01
    ジャーナル フリー
      It is obvious that pharmacists play a critical role as risk managers in the healthcare system, especially in medication treatment. Hitherto, there is not a single multicenter-survey report describing the effectiveness of clinical pharmacists in preventing medical errors from occurring in the wards in Japan. Thus, we conducted a 1-month survey to elucidate the relationship between the number of errors and working hours of pharmacists in the ward, and verified whether the assignment of clinical pharmacists to the ward would prevent medical errors between October 1-31, 2009. Questionnaire items for the pharmacists at 42 national university hospitals and a medical institute included the total and the respective numbers of medication-related errors, beds and working hours of pharmacist in 2 internal medicine and 2 surgical departments in each hospital. Regardless of severity, errors were consecutively reported to the Medical Security and Safety Management Section in each hospital. The analysis of errors revealed that longer working hours of pharmacists in the ward resulted in less medication-related errors; this was especially significant in the internal medicine ward (where a variety of drugs were used) compared with the surgical ward. However, the nurse assignment mode (nurse/inpatients ratio: 1 : 7-10) did not influence the error frequency. The results of this survey strongly indicate that assignment of clinical pharmacists to the ward is critically essential in promoting medication safety and efficacy.
  • Ying DONG, Yan ZHANG, Bingren XIANG, Haishan DENG, Jingfang WU
    原稿種別: Article
    2011 年 131 巻 4 号 p. 643-654
    発行日: 2011/04/01
    公開日: 2011/04/01
    ジャーナル フリー
      The stability and hydrolysis kinetics of a phosphate prodrug, adefovir dipivoxil, in solid formulations were studied. The stability relationship between five solid formulations was explored. An autocatalytic mechanism for hydrolysis could be proposed according to the kinetic behavior which fits the Prout-Tompkins model well. For the classical kinetic models could hardly describe and predict the hydrolysis kinetics of adefovir dipivoxil in solid formulations accurately when the temperature is high, a feedforward multilayer perceptron (MLP) neural network was constructed to model the hydrolysis kinetics. The build-in approaches in Weka, such as lazy classifiers and rule-based learners (IBk, KStar, DecisionTable and M5Rules), were used to verify the performance of MLP. The predictability of the models was evaluated by 10-fold cross-validation and an external test set. It reveals that MLP should be of general applicability proposing an alternative efficient way to model and predict autocatalytic hydrolysis kinetics for phosphate prodrugs.
  • 徳永 仁, 髙村 徳人, 緒方 賢次, 瀬戸口 奈央, 松岡 俊和, 佐藤 圭創
    原稿種別: Article
    2011 年 131 巻 4 号 p. 655-659
    発行日: 2011/04/01
    公開日: 2011/04/01
    ジャーナル フリー
      Vital-sign checks and physical assessment have been performed by physicians and nurses among medical staff in particular. However, pharmacists must also have basic skills of vital-sign checking and physical assessment to evaluate the patient condition/drug efficacy or prevent adverse reactions to drugs. To promote the acquisition of these skills, we prepared simulation programs with an emergency-care simulator, which facilitate the reproduction of excess-dose drug administration/condition changes. We used an emergency-care simulator equipped with a personal computer. General condition was established using the blinking velocity, cardiac/respiratory sounds and blood pH as parameters. As a results, concerning drug administration, the simulation programs facilitated the reproduction of symptoms related to the excess-dose insulin administration. With respect to changes in the condition, it facilitated the reproduction of asthma, hyperglycemia, and hemorrhage. This facilitated the palpation-, visual perception-, and auditory perception-mediated understanding of changes in the patient condition through fingertips and warnings/alarms on the monitor. Evaluation of the student for these program contents increased significantly (p<0.01). These programs can be downloaded via the Internet. Experience regarding excess-dose drug administration/condition changes with an emergency-care simulator is useful for checking patients' vital signs, evaluating the drug efficacy, and confirming adverse reactions to drugs. By the practice of these programs, we can teach pharmacy students how to check for vital signs (pulse palpation, auscultation, blood pressure measurement, and electrocardiography) in a school setting, not a hospital setting. Mastering these techniques may allow pharmacy students to determine the efficacy of a drug and adverse reactions.
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