臺灣博碩士論文加值系統

本研究主要目的在探討meloxicam的藥品動力學及運動是否影響要動的參數，並探究運動前、後口服meloxicam 15mg對肌肉損傷的的效果。25名健尻大學男生(20.4+-1.2歲)，自願參加本實驗，並隨機分成兩組：一組於運動前3小時服藥(n=13)，另依組於運動後立即服藥(n=12)；各組又細分為服藥組與服安慰劑組，間隔21日後服藥組改服安慰劑；服安慰劑組改服藥。以墊高跑步機成下坡10%的坡度，受試者以最大保留心跳率的70%為運動強度，跑10分中三回合，各回合間休息5分鐘。於跑步後第0、1、3、6、12、24及48小時檢查血液CK活性、LDH活性、肌紅蛋白，並測量大腿為、肌肉疼痛指數及大腿最大推蹬力，以相依樣本t考驗，考驗各時間點的各項效果；以ANOVA考驗運動前後各時間點的各項效果。同時以HPLC監測藥品血中濃度。結果發現運動對meloxicam的藥物動力學參數沒有影響，tmax=3小時。運動前服藥組肌肉疼痛指數於各測驗時間點均顯著低於服安慰劑組(P<.05)。運動後立即服藥組CK顯著小於服安慰劑組；大腿推蹬力沒有下降趨勢，並優於安慰劑組。因此，運動前服15mg meloxicam可以有效抑制運動引起的肌肉酸痛，運動後服15mg meloxicam可以減少肌肉損傷與肌力衰退的程度。

Abstract
The purpose of this study was to investigate the pharmacokinetics of meloxicam, the efficacy of exercise on pharmacokinetics, and compare the differences of muscle damage and soreness induced by eccentric running between the pre-exercise and post-exercise groups who taking 15 mg meloxicam, the non-steroid anti-inflammatory drug.
Twenty five male college students (20.4 1.2years) were participated as volunteers and randomly assigned into 2 groups; the pre-exercise (n=13) had taken the 15 mg meloxicam 3 hours before exercise and post-exercise groups (n=12) taken the medicine immediately after exercise. The subjects of each group then randomly further divided into 2 sub-groups, each sub-group either taking meloxicam or placebo and switched for another experimental trial separated by a washout period of 21 days. The exercise protocol was conducted on the treadmill with -10% and consisted of 3 inter-mitten running with 5 minutes rest in between. The subjects were asked to run during exercise session with intensity of 70% of heart rate reserved. The creatine kinase (CK), lactate dehydrogenase (LDH), myoglobin, muscle soreness index, and meloxicam concentration, muscular strength of leg press of the subjects was assessed immediately after exercise and 1st, 3rd, 6th, 12th, and 24th and 48th hours. The collected data was analyzed with t-test with repeated measured. The major results were founded as followed: 1, Pharmacokinetics of meloxicam did not affected by exercise, and tmax is 3 hr. 2, After downhill running, the subjects taking meloxicam before exercise showed the significant decrease in muscle soreness index (P< .05), while the other variables did not significantly varied. 3, the subjects taking medicine immediately after exercise indicated the significant decrease in CK and leg press did not decrease significantly. Taking meloxicam before eccentric jogging could decrease the muscle soreness, while talking after exercise would ease the muscle damage.

KEY WORDS: meloxicam, pharmacokinetics, downhill running, exercise induce muscle soreness.

目 次
口試委員與系主任簽字證書…………………………………… I
授 權 書………………………………………………………… II
中文摘要………………………………………………………… IV
英文摘要………………………………………………………… V
誌 謝………………………………………………………… VI
目 次………………………………………………………… VII
表 次………………………………………………………… X
圖 次………………………………………………………… XII
第壹章 緒論
第一節 前言………………………………………………… 1
第二節 問題背景…………………………………………… 3
第三節 研究目的…………………………………………… 7
第四節 研究假設…………………………………………… 8
第五節 研究範圍與限制…………………………………… 8
第六節 名詞操作性定義…………………………………… 9
第七節 研究的重要性……………………………………… 11
第貳章 文獻探討
第一節 運動對藥物動力學的影響………………………… 13
第二節 非類固醇消炎劑…………………………………… 15
第三節 運動引起的肌肉損傷……………………………… 21
第四節 非類固醇消炎劑與運動引起的肌肉損傷………… 25
第五節 以HPLC定性、定量血中meloxicam……………… 32
第六節 本章總結…………………………………………… 33
第參章 研究方法與步驟
第一節 研究對象…………………………………………… 35
第二節 實驗時間…………………………………………… 36
第三節 實驗地點…………………………………………… 36
第四節 實驗器材…………………………………………… 37
第五節 檢測項目與實施方法……………………………… 39
第六節 實驗流程…………………………………………… 43
第七節 統計分析與資料處理……………………………… 47
第肆章 結果
第一節 受試者基本資料…………………………………… 48
第二節 以HPLC檢測meloxicam血中濃度………………… 49
第三節 Meloxicam的藥物動力學參數…………………… 54
第四節 運動對meloxicam藥物動力學的影響…………… 55
第五節 運動前、後服藥對大腿最大推蹬力的影響……… 56
第六節 運動前、後服藥對肌肉疼痛指數的影響………… 59
第七節 運動前、後服藥對大腿圍的影響………………… 65
第八節 運動前、後服藥對血液中CK、LDH與肌紅蛋白的影響………………………………………………… 70
第伍章 討論
第一節 meloxicam的藥物動力學參數…………………… 80
第二節 運動前服藥………………………………………… 81
第三節 運動後服藥………………………………………… 84
第陸章 結論與建議
第一節 結論………………………………………………… 86
第二節 建議………………………………………………… 86
引用文獻..................................... 88
附錄一 受試者須知及參與同意書.................. 106
附錄二 受試者健康情況調查表.................... 108
附錄三 相依樣本單因子變異數分析摘要表........... 110
個人小傳 .................................... 121


表 次
表2-1 NSAIDs不同的CI50值……………………………………… 19
表2-2 以HPLC檢測血液meloxicam濃度的文獻………………… 33
表3-1 受試者實驗分組…………………………………………… 46
表4-1 受試者基本資料…………………………………………… 49
表4-2 meloxicam血清中的回收率………………………………… 51
表4-3 受試者口服meloxicam 15mg之後，藥品血中濃度………… 52
表4-4 運動後立即口服meloxicam 15mg血中meloxicam濃度…… 53
表4-5 運動前服藥組血中meloxicam濃度………………………… 54
表4-6 沒有運動組meloxicam的藥物動力學參數………………… 54
表4-7 運動後服藥組的meloxicam藥物動力學參數……………… 55
表4-8 大腿最大推蹬肌力：運動後服安慰劑、藥組……………… 55
表4-9 大腿最大推蹬肌力：運動前服安慰劑、藥組……………… 58
表4-10 左大腿酸痛指數：運動後服安慰劑、藥組……………… 60
表4-11 左大腿酸痛指數：運動前服安慰劑、藥組……………… 61
表4-12 右大腿酸痛指數：運動後服安慰劑、藥組……………… 63
表4-13 右大腿酸痛指數：運動前服安慰劑、藥組……………… 64
表4-14 右大腿圍：運動後服安慰劑、藥組……………………… 66
表4-15 右大腿圍：運動前服安慰劑、藥組……………………… 67
表4-16 左大腿圍：運動後服安慰劑、藥組……………………… 68
表4-17 左大腿圍：運動前服安慰劑、藥組……………………… 69
表4-18 血液CK值：運動後服安慰劑、藥組……………………… 70
表4-19、血液CK值：運動前服安慰劑、藥組……………………… 72
表4-20、血液LDH值：運動後服安慰劑、藥組…………………… 74
表4-21、血液LDH值：運動前服安慰劑、藥組…………………… 75
表4-22 血中肌紅蛋白值：運動後服安慰劑、藥組………………… 77
表4-23 血中肌紅蛋白值：運動前服安慰劑、藥組………………… 78
表5-1 國外學者所發現meloxicam的藥物動力學參數…………… 80



圖 次
圖2-1 NSAIDs抑制PG之生合成……………………………… 16
圖2-2 Oxicam系之NSAIDs…………………………………… 32
圖3-1 實驗流程圖……………………………………………… 44
圖4-1 內標準物與meloxicam 滯留時間圖…………………… 50
圖4-2 Meloxicam紫外光吸收圖譜…………………………… 50
圖4-3 血中meloxicam與內標準物曲線下面積比 (AUC of M/I ) 之線性迴歸圖…………………………………… 52
圖4-4 沒有運動組與運動後服藥組血中meloxicam濃度變化曲線圖…………………………………………………… 56

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