Application of Rat In Situ Single-pass Intestinal Perfusion in the Evaluation of Presystemic Extraction of Indinavir Under Different Perfusion Rates

Background/PurposeFirst-pass effect has been an important concern for oral pharmaceuticals. An in vivo system was developed for measuring different concentrations of pharmaceuticals in the portal vein and hepatic vein (via the inferior vena cava) for delineating presystemic metabolism under different perfusion rates by using indinavir as an exemplary agent.MethodsAn in situ single-pass intestinal perfusion technique was modified from previous studies to concomitantly obtain portal and hepatic venous bloods. Portal and hepatic venous samples were simultaneously taken from rats at appropriate time points using the perfusion model of 1 mg/mL indinavir at flow rates of 0.05, 0.1, 0.5 and 1.0 mL/min. The indinavir concentrations were assayed by binary-gradient high-pressure liquid chromatography with UV detection.ResultsThe mean indinavir concentrations in portal vein concentration−time profiles at different perfusion times under various flow rates were all higher than those obtained for hepatic veins. At flow rates of 0.5 and 1.0 mL/min, in particular, the area under the curve (AUC) and maximal concentration (C max) of indinavir absorption were significantly different between portal veins and hepatic veins (p < 0.05), indicating considerable hepatic involvement in the presystemic extraction of indinavir. The system also has potential for use when estimating the hepatic extraction ratio (E H) and hepatic clearance (Cl H).ConclusionThis in vivo approach could provide another useful tool for improving our basic understanding of the absorption kinetics and hepatic metabolism of pharmaceuticals under development and facilitating the clinical application of such

Use of isolated functional nuclei for study of the biochemical regulation of nuclear glutathione pool.

Use of isolated functional nuclei for study of the biochemical regulation of nuclear glutathione pool

住院處方失誤網路通報系統之建置

開方失誤(Prescribing error)乃醫藥失誤(medication error)產生的重要環節之一 ，此種失誤常經由專業執業藥師偵測並加以適當處理而及時防止。本研究探討醫學中 心藥劑部門透過建置開方失誤網路通報作業系統，使得藥師於部內網頁得以即時逐筆 線上登錄住院處方問題的成效，除就問題別做敘述性統計外，並進一步依據問題類型 、開方科部、及藥劑部門各住院調劑單位所通報失誤量做分析，期以對醫學中心住院 醫療服務之開方失誤問題加以瞭解。在九十二年七月至九十三年六月的一年研究期間 ，所通報之開方失誤量達33,426筆，佔總開方筆數1.98%，通報比例最多之處方問題 依類型別、開方科部別、調劑單位別，分別以鍵入錯誤(70.4%)、內科部(43.3%)、總 院東址住院藥局(87.0%)等項次或單位居冠，後兩者亦大致反應了其業務量及編制。 整體而言，醫師對藥師所提處方建議之平均接受率達93.5%，如就各處方問題別細部 探討，發現以「未在電腦取消應停藥醫囑」之18,783筆(56.2%)為最常見，且此項問 題之建議接受率達99.8%，顯示醫院營運效益之提昇仍有極大空間；而接受率最不理 想的項目為「出院藥與非碳寫複本不符」(26.3%)，改善方式應可朝加強醫藥溝通、 舉辦專業人員教育宣導、及調整機構開方政策等方向進行。Prescribing error is considered the key link in the occurrence of medication errors. These kinds of errors may often be detected and prevented by the pharmacy profession. By establishing a computer network reporting system in the pharmacy of a medical center, pharmacists are rendered able to key in on the intranet webpage all prescription errors they have detected from their sites of practice. This report aims to document the effect of the implementation of the computer network reporting system. Besides the descriptive analysis of the types of prescription errors, we further analyze the errors according to the types of errors, prescribing departments, and the amount of reported errors in each pharmacy divisions, in the hope to further understand the causes of this type of errors. Between July, 2003 and June, 2004, a total of 33,426 medication orders (1. 98% of total prescription orders) were reported to be problematic. The most frequent errors according to the types of errors, prescribing departments, and dispensing departments, are computer entry errors (70.4%) , department of internal medicine (43.3%) and inpatient pharmacy of the East wing of NTUH (87.0%), respectively. The latter two percentages basically reflect the amount of service. The physicians' acceptance rate for the pharmacist's intervention on the average reaches 93.5%. To look into this further, "failure to discontinue the order on the computer" is the number one reason for pharmacist's intervention (18, 783 orders, 56.2% ) on the list, and the acceptance rate of doctors is also high (99.8%). This may imply that there's still room for improvement in terms of the efficiency of hospital management The least accepted intervention was " inconsistency between computerized and written versions of discharge medication orders" (26.3%), efforts should be aimed at improving the communication between physicians and pharmacists, education campaigns for medical and pharmacy professionals, as well as adjustment of prescribing policies

Detecting Drug-Drug Interactions in Medication Profiles of Psychiatric Inpatients: A Two-Stage Approach

A two-stage evaluation methodology was developed to detect drug-drug interactions (D-DIs) of moderate and major severity in a psychiatric inpatient population. During a 3-month study period, the medication orders prescribed for 152 psychiatric inpatients in two psychiatric wards of a medical center were examined. A primary assessment of patients' reactions due to drug interactions was carried out by physicians who were provided with pertinent drug interaction monographs. A secondary assessment was performed by a three-member committee using explicit criteria to decide which reactions were actual D-DIs. Potential moderate or major severity D-DIs were identified in 79 (52.0%) of the 152 patients. A total of 130 potential interactions were detected in 339 (63.1%) of the 537 medication profiles. Actual D-DIs were seen in two patients (1.3%) who were prescribed trazodone with chlorpromazine and doxepin with paroxetine, respectively. The discrepancy between incidences of potential and actual D-DIs suggests that the method was sensitive in the detection and prudent in the assessment of D-DIs

合用trazodone與chlorpromazine併發坐立性低血壓：一例報告

在臨床之藥物治療上，藥品之併用是常見的現象，但如果併用藥品間產生不良的藥品 交互作用，輕者常須入院治療或造成住院天數的延長，重者則甚至危及生命或死亡。 因此，醫療人員在給病人用藥時，應時常保持對藥品交互作用的警覺性，以確保藥品 有效及安全的使用。本文欲藉由報告一例因併用trazodone與chlorpromazine後而產 生直立性低血壓，且伴隨有嗜睡、頭暈、步態不穩及跌倒等現象的住院案例，盼能提 供各醫療單位在使用這種藥品組合治療病患時，留意低血壓相關副作用的發生，以期 達到預防、及早偵測或處置之效。Individual patients prescribed with multiple therapeutic agents are commonly seen in various clinical settings. The concurrent use of two or more agents may lead to undesired adverse drug interactions, resulting in superfluous hospital admissions, prolonged hospital stay, or even life- threatening events and mortalities. To ensure the effective and safe use of drugs, health care professionals should always be alert to any possibility of significant drug interactions occurred on their patients. We report a psychiatric inpatient who had developed postural hypotension , accompanied by symptoms of drowsiness, dizziness, unsteady gait, and fall, four days following the combined use of trazodone and chlorpromazine during hospitalization. We hope that the case will enhance professionals' awareness of this drug interaction pair and that such events could be detected and managed timely and appropriately

社區藥局實習之教學演進

台大醫學院藥學系之社區藥局實習，過去採取與連鎖藥局建教合作方式，開課已屆十 年，選修之學生累積有一百七十八人，約佔學生總數之31.8%，參與藥局家數累計六 十三家。本文試圖藉由審視過去十年課程之演進，客觀地探討實施過程中，所潛藏的 困難、問題與改進之道。在國內其他藥學校相繼、甚或參照此建教合作模式開設課程 之際，我們深覺在相關課程之搭配、教學藥局與實習指導藥師之評選、及對實習指導 藥師之適當鼓勵等方面，應適時加以檢討與建立制度，使社區藥局實務之教學，不再 被國內以往之藥學教育體制所忽視，在台灣能早日成為藥師養成教育重要之一環。 The Community Pharmacy Practice Externship course at the School of Pharmacy, National Taiwan University, offered through collaboration with chain pharmacies, has been in place for the years. A total of 178 students (31.8%) and 63 pharmacies have participated in the course thus far. Course development is reviewed, and the difficulties and problems encountered over the past years are identified with a view to strategies for future improvement. To date, several pharmacy schools in Taiwan have implemented a similar arrangement so that they can offer it as an elective course for students. Room still exists for improvement, such as the addition of community pharmacy related courses, the use of criterion- guided selection of externship sites and preceptors, and the provision of appropriate encouragement for participating pharmacists. It is hoped that near future community pharmacy practice courses such as this can be acknowledged by pharmacy educators as an integral part of professional training

Lipid-Mediated Preferential Localization of Hypericin in Lipid Membranes

Subcellular localization of a photosensitizer is critical to its therapeutic outcome during photodynamic therapy (PDT). We delineated the distribution of hypericin, a new generation photosensitizer, in model membrane systems to identify the operating principles of its subcellular accumulation. Results from fluorescence microscopy indicated preferential incorporation of hypericin in lipid of giant unilamellar vesicles. Monolayer fluorescence measurements further identified cholesterol as the key determinant for the observed selectivity of hypericin. The emission spectra of hypericin in lipid monolayers varied in a lipid-dependent manner and Stoke’s shift behavior suggests that hypericin may form closely packed structure with cholesterol. Overall, our data lead to the conclusion that cholesterol is the major origin of the selectivity for hypericin in membrane systems. A hypothetical model depicting the intracellular and intravascular co-transport of hypericin and cholesterol because of their high affinity is presented