簡易檢索 / 詳目顯示

回結果列表
研究生： 蔡欣潔
Hsin-Chieh Tsai
論文名稱： 運動對Meloxicam藥物動力學的影響及Meloxicam對運動引起的肌肉酸痛的效果
Effects of Exercise on Pharmacokinetics of Meloxicam and the Efficacy of Meloxicam on Exercise Induced Muscle Soreness
指導教授： 方進隆
Fang, Chin-Lung
學位類別： 博士
Doctor
系所名稱： 體育學系
Department of Physical Education
論文出版年： 2007
畢業學年度： 95
語文別： 中文
論文頁數： 121
中文關鍵詞： 藥物動力學 、下坡跑 、運動引起的肌肉酸痛 、meloxicam
英文關鍵詞： pharmacokinetics, downhill running, exercise induce muscle soreness, meloxicam
論文種類： 學術論文
相關次數： 點閱：377  下載：10 
分享至:
查詢本校圖書館目錄 查詢臺灣博碩士論文知識加值系統 勘誤回報

    • 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

    何應志，許美智。(2001)。運動對藥物動力學的影響。大專體育，52，68-74。

    林正常。(1993)。運動科學與訓練：運動教練手冊（增訂二版）。台北縣：銀禾文化。

    林威秀。(1998)。按摩、伸展、Meloxicam對延遲性肌肉酸痛的影響。國立體育學院運動科學研究所碩士論文。

    陳忠慶。 (1996)。最大自主等速離心收縮對延遲性肌肉酸痛恢復的影響。國立台灣師範大學體育研究所碩士論文。

    陳忠慶。(2002)。重複訓練效應對肌肉損傷的影響。國立台灣師範大學體育研究所博士論文。

    許美英。(1997)。隨機雙盲對照臨床研究比較Meloxicam 7.5mg 與 Diclofenac 長效錠100 mg 對臺灣地區退化性關節炎病人28天治療的療效和安全性。國立成功大學臨床藥學研究所碩士論文。

    Akca, T., Colak, T., Kanik, A. Yaylak, F., Caglikulekci, M., Aydin S. (2004). The Effect of preoperative intravenous use of tenoxicam: A prospective, double-blind, placebo-controlled study, Journal of Investigative Surgery, 17, (6), 333 - 338

    Armstrong, R. B. (1984). Mechanisms of exercise-induced delayed onset muscular soreness：A brief review. Medicine and Science in Sports and Exercise, 16, 529-538.

    Armstrong, R.B., Ogilvie, R.W., Schwane, J. A. (1983). Eccentric exercise-induced injury to rat skeletal muscle. Journal of Applied Physiology, 54, 80-93.

    Baldwin, A. C., Stevenson, S. W., Dudley, G. A. (2001). Non-steroidal anti-inflammatory therapy after eccentric exercise in healthy older individuals. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences 56, M510-M513.

    Barlas, P., Craig J. A., Robinson, J., et al. (2000). Managing delayed-onset muscle soreness: lack of effect of selected oral systemic analgesics. Archives of Physical Medicine and Rehabilitation, 81, 966-972.

    Berry, C. B., Moritain, T., & Tolson, H. (1990). Electrical activity and soreness in muscles after exercise. American Journal of Physical Medicine and Rehabilitation, 69, 60-66.

    Bourgeois, J., MacDougall, D., MacDonald, J., et al. (1999). Naproxen does not alter indices of muscle damage in resistance-exercise trained men. Medicine & Science in Sports & Exercise, 31,4-9.

    Brown, S. J., Chil, R. B., S. H., Donnelly, A. E. (1997). Exercise-induced skeletal muscle damage and adaptation following repeated bouts of eccentric muscle concentrations. Journal of Sports Science, 15(2), 215-222.

    Byrnes, W. C., Clarkson, P. M., White, J. S., Hsieh, S. S., and Fryman, P. N. (1985). Delayed onset muscle soreness following repeated bouts of downhill running. Journal of Applied Physiology, 59, 710-715.

    Chen, T. C. & Hsieh, S. S. (2000). The effects of repeated maximal voluntary isokinetic eccentric exercise on recovery from muscle damage. Research Quarterly for Exercise and Sport, 71(3), 260-266.

    Chen, T. C. & Hsieh, S. S. (2001). Effects a 7-days eccentric training period on muscle damage and inflammation. Medicine and Science in Sports and Exercise, 33(10), 1732-1738.

    Clarkson, P. M. & Hubal, M. J. (2002). Exercise-induced muscle damage in humans. American Journal of Physical Medicine & Rehabilitation, 81(11), S52-S69.

    Clarkson, P. M., Nosaka, K. and Braun, B. (1992). Muscle function after exercise-induced muscle damage and rapid adaptation. Medicine and Science in Sports and exercise, 24, 512-520.

    Clarkson, P. M., & Tremblay, I. (1988). Exercise-induced muscle damage, repair, and adaptation in humans. Journal of Applied Physiology, 65(1), 1-6.

    Cryer, B. & Feldman, M. (1998). Cyclooxygenase-1 and cyclooxygenase-2 selectivity of widely used nonsteroidal anti-inflammatory drugs. The American Journal of Medicine, 104(5), 413-421.

    Davies, N.M., Skjodt, N.M. (1999). Clinical pharmacokinetics of meloxicam. A cyclo-oxygenase-2 preferential nonsteroidal anti-inflammatory drug. Clinical Pharmacokinetics, 36(2), 115-26.

    Dasandi, B., Shivaprakash , Saroj H., Bhat, K.M. (2002). LC determination and pharmacokinetics of meloxicam. Journal of Pharmaceutical and Biomedical Analysis, 28, 999-1004.

    Dequeker, J., Hawkey, C., Kahan, A., Steinbruck, K., Alegre, C., Baumelou, E., et al. (1998). Improvement in gastrointestinal tolerability of the selective cyclooxygenase (COX)-2 inhibitor, meloxicam, compared with piroxicam: results of the Safety and Efficacy Large-scale Evaluation of COX-2 inhibiting Therapies (SELECT) trial in osteoarthritis. The British journal of rheumatology, 37, 946-951.

    Donnelly, A. E., Maughan, R. J., Whiting, P. H. (1990). Effects of ibuprofen on exercise-induced muscle soreness and indices of muscle damage. British Journal of sports Medicine, 24, 191-195.

    Ebbeling, C. B., & Clarkson, P. M. (1089). Exercise-induced muscle damage and adaptation. Sports Medicine, 7, 207-234.

    Ebbeling, C. B., & Clarkson. P. M. (1990). Muscle adaptation prior to recovery following eccentric exercise. European Journal of Applied Physiology, 60, 26-31.

    Edwards, R.H.T., Hill, D. K., Jones D. A., & Merton, P. A. (1977). Fatigue of long duration in human skeletal muscle after exercise. Journal of Physiology, 222, 769-778.

    Elbary A. A., Foda N., Elkhateeb M. (2001). Reversed Phase Liquid Chromatographic Determination of Meloxicam in Human Plasma and its Pharmacokinetic Application. Analytical Letters, 34(7), 1175-1187.

    Engelhardt, M., Pairet M. (1996). Distinct isoforms(COX-1 and COX-2) of cyclooxygenase: possible physiological and therapeutic implications. Fundamental & Clinical Pharmacology,10(1), 1-17.

    Farquhar, W.B., Morgan, A.L., Azmbraski, E.J. (1999). Effects of acetaminophen and ibuprofen on renal function in the stressed kidney. Journal of Applied Physiology, 86 (2), 598-604.

    Friden, J., & Leiber, R. L. (1998). Segmental muscle fiber lesions after repetitive eccentric contractions. Cell and Tissue Research, 293, 165-171.

    Friden, J., Sjostrom, M., & Ekblom, B. (1983). Myofibrillar damage following intense eccentric exercise in man. International Journal of Sports Medicine, 4, 170-176.

    Gates, B.J., Nguyen, T.T., Setter, S.M., Davies, N.M., (2005). Meloxicam: a reappraisal of pharmacokinetics, efficacy and safety. Expert Opinion on Pharmacotherapy, 6(12), 2117-40.

    Gibala, M. J., MacDougal, J. D. Tarnopolsky, M. A, (1995). Changes in human skeletal muscle ultrastructure and force production after acute resistance exercise. Journal of Applied Physiology, 78, 702-708.

    Greene, G. A. (2001). Understanding NSAIDs: from aspirin to COX-2.Clinical Cornerstone, 3(5):50-56.

    Griffin M. (1998). Epidemiology of nonsteroidal anti-inflammatory drug-associated gastrointestinal injury. The American Journal of Medicine, 104 (Supplement, 3A), 23S-29S.

    Hasson, S. M., Daniels, J. C., Divine, J. G. (1993). Effect of ibuprofen use on muscle soreness, damage, and performance: a preliminary investigation. Medicine & Science in Sports & Exercise, 25, 9-17.

    Hawkey, C., Kahan, A., Steinbruck, K., Alegre, C., Baumelou, E., Begaud, B., et al. (1998).Gastrointestinal tolerability of meloxicam compared to diclofenac in osteoarthritis patients. International MELISSA Study Group. British Journal of Rheumatology, 37, 937 - 945.

    Henry, D., Page, J., Whyte, I. (1997). Consumption of nonsteroidal anti-inflammatory drugs and the development of functional renal impairment in elderly subjects: results of a case-controlled study. British Journal of Clinical Pharmacology, 44, 85-90.

    Hernandez-Diaz, S. & Garcia-Rodriguez, G. (2001). Epidemiologic assessment of the safety of conventional nonsteroidal anti-inflammatory drugs. The American Journal of Medicine, 110 (Supplement 3A): 20S-27S.

    Horattas, C. M., Evans S., Sloan-Stakleff, D. K., Lee, C. and Snoke, W. J. (2004). Does preoperative rofecoxib (Vioxx) decrease postoperative pain with laparoscopic cholecystectomy? The American Journal of Surgery, 188, (3), 271-276.

    Hyatt, J.-P. K., & P. M. Clarkson.(1998). Creatine kinase release and clearance using MM Variants following repeated bouts of eccentric exercise. Medicine and Science in Sports and Exercise, 30(7), 1059-1065.

    Jamurtas, A. Z., Fatouros, I. G., Buckenmyer, P., Kokkinidis, E., Taxildaris, K., Kambas, G. et al. (2000). Effects of plyometric exercise on muscle soreness and plasma creatine kinase levels and its comparison with eccentric and concentric exercise. Journal of Strength and Conditioning Research, 14, (1), 68-74.

    Jerome, G.M., Diquelou, A., Laroute, V., Lees, P., and Toutain, P.L., (2005). Pharmacokinetic/pharmacodynamic modelling of NSAIDs in a model of reversible inflammation in the cat British Journal of Pharmacology, 146, 642-653.

    Jones, D. A., Newham, D. J., Round, T. M., & Tolfree, S. E. (1986). Experimental human muscle damage morphological changes in relation to other indices of damage. Journal of Physiology, 438, 173.

    Koller, A. (2005). Creatine phosphokinase and muscle damage. Medicine and Science in Sports and Exercise, 37(1):166.

    Koch, M., Dezi, A, Ferrario, F., et al. (1999). Prevention of nonsteroidal anti-inflammatory drugs. New England Journal of Medicine, 340(24): 1888-1899.

    Leiber, R. L. and Friden, J. (1993). Muscle damage is not a function of muscle force but active muscle strain. Journal of Applied Physiology 74, 520-526.

    Leiber, R. L. & Friden, J. (1998). Selective damage of fast glycolytic muscle fibers with eccentric contraction of the rabbit tibialis anterior. Acta Physiologica Scandinavian, 133, 587-588.

    Leiber, R. L., Thornell, L.E., Friden, J.(1996). Muscle cytoskeletal disruption occurs within the first 15 minutes of cyclic eccentric contraction. Journal of Applied Physiology, 80, 278-284.

    Lieber, R. L., Woodburn, T. M., Friden, J. (1991). Muscle damage induced by eccentric contractions of 25% strain. Journal of Applied Physiology, 70, 2498-2507.

    Malmsten, C. L. (1986). Prostaglandins, thromboxanes, and leukotrienes in inflammation. The American Journal of Medicine, 80, 11-17.

    Manfredi, T.G., Fielding, R. A., O’Reilly, K.P., et al. (1991). Plasma creatine kinase activity and exercise-induced muscle damage in older men. Medicine and Science in Sports and Exercise, 23, 1028-1034.

    Marsh, T. D., Garnett, W. R., Poynor, W. J. & Pellock, J. M. (1983) Effects of exercise on valproic acid pharmacokinetics. Clinical Pharmacy, 2, 62-64

    Maughan, R. J., Donnely, A. E., Gleeson, M., Whiting, P.H., Walker, K. A., and Clough, P. J. (1989). Delayed-onset muscle damage and lipid peroxidation in man after a downhill run. Muscle and Never, 12, 332-336.
    McBride, T. A., Stockert, B. W., Gorin, F. A., et al. (2000). Stretch-activated ion channels contribute to membrane depolarization after eccentric contractions. Journal of Applied Physiology, 88, 91-101.

    Michaut, A., Babault, N. and Pousson, M. (2004). Specific effects of eccentric training on muscular fatigability. International Journal of Sports Medicine, 25, 278-283.

    Mitchell, J. A., Akarasereenont, P., Thiemermann, C., et al. (1993). Selectivity of nonsteroidal anti-inflammatory drugs as inhibitors of constitutive and inducible cyclooxygenase. Proceedings of the National Academy of Sciences of the United States of America, 90, 11693-11697.

    Micalos, S. P., Marino, E. F. and Kay, D. (2004). Reduced muscle pain intensity rating during repeated cycling trials. Journal of Sports Science and Medicine, 3, 70-75.

    Miller, P. C., Bailey, S. P., McInnis, K. R., Hall, E. E. (2003). Comparison of protease and NSAID supplementation on muscle soreness and pain threshold following downhill running. Medicine and Science in Sports and Exercise, 35, (5) S197-201.
    Morgan, D. L., Allen, D.G., (1999). Early events in stretch-induced muscle damage. Journal of Applied Physiology, 87(6), 2007-2015.
    Neal, M. J. (1987). Medical pharmacology at a glance, (pp.66), Oxford, Blackwell scientific publication.

    Newham, D. J., Mills K. R., Quigley B. M., Edwards R. H. T., (1983). Pain and fatigue following concentric and eccentric contractions. Clinical Science, 64, 55-62.

    Newham, D. J. (1988). The consequences of eccentric contraction and their relationship to delayed onset muscle pain. European Journal of Applied Physiology, 57, 353-359.

    Nosaka, K., & Clarkson, P. M. (1992). Relationship between post-exercise plasma CK elevation and muscle mass involved in the exercise. International Journal of Sports Medicine, 13, 471-475.

    Nosaka, K, & Clarkson. P. M. (1994). Plasma enzyme response after a subsequent bout of eccentric exercise. European Journal of Applied Physiology, 69, 492-497.

    Nosaka, K., & Clarkson, P.M. (1995). Muscle damage following repeated bouts of high force eccentric exercise. Medicine and Science in Sports and Exercise, 27, 1263-1269.

    Nosaka, K., & P. M. Clarkson. (1996). Variability in serum creatine kinase response after eccentric exercise of the elbow flexors. International Journal of Sports Medicine,17, 120-127.

    Nosaka, K., & Newton, M. (2002). Concentric or eccentric training effect on eccentric exercise-induced muscle damage. Medicine and Science in Sports and Exercise, 34(1), 63-69.

    O’Grady, M., Hackney, A. C., Schneider, K., Bossen, E., Steinberg, K., Douglas, J. M., Murray, JR. W. and Watkins, W. D. (2000). Diclofenac sodium (Voltaren) reduced exercise-induced injury in human skeletal muscle. Medicine & Science in Sports & Exercise, 32(7), 1191-1196

    O’Reilly, K. P., Warhol, M. J., Fielding, R. A. Et al. (1978). Eccentric exercise-induced muscle damage impairs muscle glycogen repletion. Journal of Applied Physiology, 63, 252-256.

    Pairet, M., Ryn, van, Schierok, H., Mauz, A., Trummlitz, G., Engelhardt, G. (1998) Differential inhibition of cyclooxygenases-1 and -2 by meloxicam and its 4'-isomer. Inflammation Research 47, 270-276.

    Page, J. Henry, D. (2000). Consumption of NSAIDs and the development of congestive heart failure in elderly patients: an under-recognized public health problem. Archives of Internal Medicine, 160, 777-784.

    Patel, N. A., Finlay, U. K., Schyra, C. K., Jones, C. C., Black, E. R., Dullye, J. L. et al. (2002). Use of general anesthetic only vs general anesthetic combined with paravertebral block for perioperative pain management after first rib resection. Proc (Bayl Univ Med Cent), 15(4), 374–375.

    Patel, T. J., Cuizon, D., Mathieu-Costello, O., et al. (1998). Increased oxidative capacity does not protect skeletal muscle fibers from eccentric contraction-induced injury. American Journal of Physiology, 274 (5-2), R1300-1308.

    Peeze Binkhorst, F.M., Slaaf, D.W., Kuipers, H., Tangelder, G. J. and Reneman, R. S. (1990). Exercise-induced swelling of rat soleus muscle: its relationship with intramuscular pressure. Journal of Applied Physiology, 69, 67-73.

    Perneger, T.V., Whelton, P.K., Klag, M.J. (1994). Risk of kidney failure associated with the use of acetaminophen, aspirin, and nonsteroidal anti-inflammatory drugs. New England Journal of Medicine, 331, 1675-1678.

    Pizza, F.X., Cavender, D., Stockard, A., et al. (1999). Anti-inflammatory doses of ibuprofen effect on neutrophils and exercise-induced muscle injury. International Journal of Sports Medicine, 20(2), 98-102.

    Polat, O., Karaman, I. A., Durmus, E. (2004). Effects of preoperative ibuprofen and naproxen sodium on orthodontic pain. The Angle Orthodontist, 75, (5), 791–796.

    Porta, V., Ferraz, Humberto G., Souza, T., Kano, E. K., Serra, C. (2005), Determination of meloxicam in human plasma by HPLC. Revista Brasileira de Ciências Farmacêuticas, 41, (2), 215-222.

    Po

    QR CODE