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系統識別號 U0026-1607201323184400
論文名稱(中文) 臺灣門診老年癲癇病患抗癲癇藥物之潛在藥物交互作用評估
論文名稱(英文) Assessment of Potential Drug-Drug Interaction with Antiepileptic Drugs in Ambulatory Elderly Patients with Epilepsy in Taiwan
校院名稱 成功大學
系所名稱(中) 臨床藥學與藥物科技研究所
系所名稱(英) Institute of Clinical Pharmacy and Pharmaceutical sciences
學年度 101
學期 2
出版年 102
研究生(中文) 王美文
研究生(英文) Mei-Wen Wang
學號 s66001010
學位類別 碩士
語文別 中文
論文頁數 132頁
口試委員 指導教授-高雅慧
口試委員-賴明亮
口試委員-黃欽威
口試委員-葉鳳英
中文關鍵字 老年  抗癲癇藥物  藥物交互作用  危險因子 
英文關鍵字 elderly  epilepsy  drug-drug interaction  risk factors 
學科別分類
中文摘要 研究背景:抗癲癇藥物參與許多肝臟酵素代謝的過程,可能會造成藥物交互作用及相關藥物不良反應。老年人為癲癇的好發族群,又常因其他共病症而需併服多種藥物,因此藥物交互作用一直是老年癲癇病患治療的難題。然而目前對於老年癲癇病患之潛在藥物交互作用的研究仍相當有限,且缺乏具體量化此族群之藥物交互作用風險程度及探討其危險因子的分析。
研究目的:評估並量化臺灣老年癲癇病患潛在藥物交互作用風險程度及其危險因子。
研究方法:以全民健康保險資料庫進行回溯性世代研究。納入2005年至2009年間年齡大於65歲、新診斷癲癇且至少於門診使用一種抗癲癇藥物之老年癲癇病患,評估抗癲癇藥物開始使用後一年內之潛在藥物交互作用風險程度。納入Drug Interaction Facts 2013、Lexi-Comp OnlineTM或Micromedex等參考文獻定義為和抗癲癇藥物具有潛在交互作用之藥品。以併用藥物總處方天數除以抗癲癇藥物使用天數之DDI score,做為抗癲癇藥物潛在藥物交互作用風險程度之量化指標。分析病患年齡、性別、就醫紀錄(指標年度、醫院層級、就醫科別、主要照護醫師年資)、共病症等資訊,以線性迴歸模式確認抗癲癇藥物潛在藥物交互作用之危險因子。
研究結果:共納入5,785 位老年癲癇病患,平均年齡為76.61±7.15歲,55.9%為男性。平均追蹤時間為259.63 (±105.62) 天。研究對象在追蹤期間至少暴露一種抗癲癇藥物潛在藥物交互作用(AED-DDIs) 的發生率為64.9%,平均DDI score為0.68 (±0.80),以phenytoin(0.94) 及carbamazepine(0.99)分數最高。在危險因子方面,傳統抗癲癇藥物使用者[β=0.72; 95% CI: 0.65, 0.78]、非神經科追蹤[β=0.07 (95% CI: 0.03, 0.12)]、過去三個月內使用超過6種慢性疾病藥物 [β=0.20 (95% CI: 0.15, 0.25)]、中風[β=0.08 (95% CI: 0.04, 0.13)]、高血壓[β=0.22 (95% CI: 0.18, 0.26)]、缺血性心臟病[β=0.10 (95% CI: 0.06, 0.15)]或慢性阻塞性肺病[β=0.05 (95% CI: 0.01, 0.10)]病史的病患,其DDI score顯著較高。
結論: 臺灣老年癲癇病患潛在藥物交互作用相當普遍。老年癲癇病患潛在藥物交互作用之危險因子包括傳統抗癲癇藥物、非神經科、多重用藥、心血管疾病、慢性阻塞性肺病。臨床工作者應更加重視老年癲癇病患藥物交互作用的評估與並加以預防。
英文摘要 Background: Because some antiepileptic drugs (AEDs) have great involvements of hepatic enzymes and can affect metabolic processes of drugs, potiential drug-drug interaction (DDI) is one of the main concerns in epileptic treatment. Elderly patients who often take concomitant medications were especially at high risk of drug interactions. However, limited information was available from previous studies about AED-DDIs in this group. Factors associated with higher risk of AED-DDIs have not been identified.
Purpose: The study aimed to evaluate the degree and associated risk factors of drug–drug interactions with antiepileptic drugs ( AED-DDIs) in elderly patients with epilepsy in Taiwan.
Method: A retrospective cohort study was conducted by using Taiwan’s National Health Insurance Research Database (NHIRD). Patients aged 65 or older with epilepsy defined by ICD-9 code 345 from 2005 to 2009 were included. From the date of AEDs initiation, patients were followed until the end of one year, discontinuation, switch/add-on, or disenrollment. Medications with AED-DDIs were defined by Drug Interaction Facts 2013, Lexi-Comp OnlineTM, and Micromedex. DDI score were calculated as primary indicator of AED-DDIs degree, defining as days of medication with AED-DDIs supplied divided by follow-up days. Multivariate linear regression models were used to identify risk factors associated with AED-DDIs.
Result: A total of 5,785 elderly patients with epilepsy were identified with mean age was 76.61 (±7.15) years and 55.9% were male. The mean DDI score of all patients was 0.68 (±0.80), and the highest score were found in patient receiving phenytoin (0.94) and carbamazepine (0.99). Individuals receiving traditional AEDs [β=0.72; 95% CI: 0.65, 0.78], being cared by specialist other than neurologist [β=0.07; 95% CI: 0.03, 0.12], receiving more than 6 drugs for chronic conditions [β=0.20 (95% CI: 0.15, 0.25)], and comorbid condition of stroke [β=0.08 (95% CI: 0.04, 0.13)], hypertension [β=0.22 (95% CI: 0.18, 0.26)], ischemic heart disease [β=0.10 (95% CI: 0.06, 0.15)] and chronic obstructive pulmonary disease [β=0.05 (95% CI: 0.01, 0.10)] were associated with higher DDI score.
Conclusion: A high degree of AED-DDIs in elderly patients with epilepsy warrants clinical attentions. Numbers of risk factors were identified and can be strong grounds for future investigations and policy decisions.
論文目次 中文摘要 I
Abstract III
誌謝 V
目錄 VII
表目錄 X
圖目錄 XI
第一篇、臺灣門診老年癲癇病患抗癲癇藥物之藥物交互作用評估 1
第一章、研究背景 1
第二章、文獻回顧 3
第一節、老年癲癇簡介 3
第二節、抗癲癇藥物簡介 5
第三節、抗癲癇藥物交互作用及其重要 9
第四節、老年病患的藥物交互作用與危險因子 15
第五節、藥物交互作用參考文獻資料 17
第六節、藥物交互作用之相關研究 21
第三章、研究目的及重要性 25
第一節、研究目的 25
第二節、研究重要性 25
第四章、研究方法 26
第一節、研究設計 26
第二節、研究名詞、研究變項與操作定義 31
第三節、資料處理流程 39
第四節、統計分析 40
第五章、研究結果 43
第一節、研究對象納入、排除 43
第二節、研究對象基本資料 44
第三節、指標抗癲癇藥物型態 48
第四節、潛在藥物交互作用型態 48
第五節、抗癲癇藥物交互作用危險因子 56
第六節、敏感度分析 65
第六章、討論 68
第一節、研究對象納入與排除條件之分析 68
第二節、抗癲癇藥物型態 69
第三節、抗癲癇藥物交互作用型態 70
第四節、抗癲癇藥物交互作用危險因子 77
第五節、研究限制 81
第七章、結論與建議 82
第八章、未來研究方向 83
第二篇、臨床藥事服務-門診癲癇病患藥事服務 84
第一章、服務背景 84
第二章、臨床服務設計與執行 86
第一節、服務的目的 86
第二節、服務執行方法 86
第三章、臨床服務執行結果 88
第一節、服務對象基本資料 89
第二節、服務對象抗癲癇藥物知識與用藥情形 90
第四章、討論 93
第一節、抗癲癇用藥知識 93
第二節、癲癇病患自行用藥情況 94
第三節、癲癇病患藥品資訊來源與需求 95
第四節、抗癲癇用藥衛教資料編輯 96
第五章、感想與建議 97
參考文獻 98
附錄 102
附錄一、抗癲癇藥物交互作用 102
附錄二、門診癲癇病患藥事服務問卷 108
附錄三、抗癲癇藥物與中藥之藥物交互作用 111
附錄四、抗癲癇用藥手冊 112

表目錄
第一篇、 臺灣門診老年癲癇病患抗癲癇藥物之藥物交互作用評估
表2- 1、抗癲癇藥物交互作用相關之藥品動態學性質 13
表2- 2、抗癲癇藥物與相關肝臟代謝酵素之關係 14
表2- 3、藥物交互作用分類對照表 18
表2- 4、各文獻藥物交互作用分級對照 19
表2- 5、Drug Interaction Facts藥物交互作用分級表 20
表2- 6、Lexi-Comp OnlineTM藥物交互作用分級表 20
表2- 7、抗癲癇藥物交互作用研究比較 24
表4- 1、各檔案間串檔變項說明 27
表4- 2、抗癲癇藥品定義與ATC 碼對照 34
表4- 3、本研究相關疾病定義與診斷碼(ICD-9-CM) 35
表4- 4、地區分類 36
表4- 5、併用藥品 37
表5- 1、研究對象基本資料 45
表5- 2、研究對象就醫資料 46
表5- 3、研究對象共病症資料 47
表5- 4、抗癲癇藥物型態之年齡性別分布 51
表5- 5、研究對象依指標抗癲癇藥物之潛在藥物交互作用分佈情況 55
表5- 6、有潛在藥物交互作用者之藥物交互作用分佈情況 55
表5- 7、羅吉氏回歸分析暴露潛在藥物交互作用之危險因子 59
表5- 8、線性回歸分析潛在藥物交互作用風險程度之危險因子 62
表5- 9、敏感度分析: 潛在藥物交互作用之危險因子 67
表5-10、敏感度分析: 潛在藥物交互作用風險程度之危險因子 67
表6- 1、本研究與過去研究比較 75
第二篇、臨床藥事服務-門診癲癇病患藥事服務
表3- 1、臨床藥事服務對象基本資料 89

圖目錄
第一篇、臺灣門診老年癲癇病患抗癲癇藥物之藥物交互作用評估
圖4-1、研究流程 30
圖4-2、潛在藥物交互作用計算方法 33
圖5-1、研究對象納入與排除情況 43
圖5-2、指標年度之抗癲癇藥物型態分佈 50
圖5-3、抗癲癇藥物型態之年齡性別分佈 50
圖5-4、各指標年度研究對象潛在藥物交互作用發生率 52
圖5-5、研究對象潛在藥物交互作用發生率之年齡與性別分布 52
圖5-6、各指標藥物研究對象潛在藥物交互作用發生率 53
圖5-7、研究對象之併用藥物型態分佈 53
圖5-8、研究對象各年度之抗癲癇藥物潛在藥物交互作用發生率比較 54
圖5-9、研究對象各年度之抗癲癇藥物潛在藥物交互作用風險程度比較 54
圖6-1、抗癲癇藥物潛在藥物交互作用發生率與其他文獻比較 73
圖6-2、抗癲癇藥物交互作用風險程度 73
第二篇、臨床藥事服務-門診癲癇病患藥事服務
圖 2-1、臨床藥事服務執行流程 87
圖3-1、臨床藥事服務對象納入與排除情況 88
圖3-2、服務對象抗癲癇藥物知識分佈 91
圖3-3、服務對象自行併用藥物 91
圖3-4、服務對象抗癲癇藥物知識來源 92
圖3-5、服務對象抗癲癇藥物問題與疑慮 92
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