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題名 | 中藥補陽還五湯作用於阿斯匹靈在大白鼠體內藥物動力學與藥效學的交互作用=Herb-drug Interaction of Bu-yang-huan-wu-tang on the Pharmacokinetics and Pharmacodynamics of Aspirin in Rats |
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作者姓名(中文) | 蔡東湖; | 書刊名 | 中醫藥年報 |
卷期 | 3 2014.12[民103.12] |
頁次 | 頁(15)1-(15)25 |
分類號 | 414.5 |
關鍵詞 | 補陽還五湯; 藥物動力學; 草藥-藥物交互作用; 阿斯匹靈; Bu-yang-huan-wu-tang; Pharmacokinetics; Herb-drug interaction; Aspirin; Stroke; |
語文 | 中文(Chinese) |
中文摘要 | 本計畫擬評估中藥補陽還五湯是否影響抗血小板凝集藥物阿斯匹靈在大白鼠體內藥物動力學的變化。阿斯匹靈因具有抗血小板凝集作用,非常普遍使用於臨床上預防缺血性中風和短暫性腦缺血發作 (TIA)。補陽還五湯含有補氣(黃耆)和活血化瘀(當歸、川芎、赤芍、丹参、桃仁、紅花等)的中藥,自清朝常使用於改善中風後遺症的方劑。若中風或 transient ischemic attack (TIA)患者同時併服補陽還五湯再加服用西藥阿斯匹靈治療和預防第二次中風,是否可能造成出血的風險增加 ? 為了深入了解補陽還五湯和西藥阿斯匹靈二者在生物體內的交互作用和代謝情況,實驗設計將實驗組大鼠給予補陽還五湯 (100 mg/kg, po)連續口服五天,對照組則給予空白基劑五天,第六天皆以股靜脈注射阿斯匹靈 (10, 30 或 100 mg/kg, iv)。動物手術主要藉由微透析動物模式,採集血液及腦部透析液,將微透析探針分別插入頸靜脈及腦部紋狀體,連續採集未結合蛋白質型態阿斯匹靈及代謝物水楊酸,以高效液相層析儀分析其濃度,並觀察及比較其藥物動力學變化。藥物動力學研究結果顯示,給予大鼠補陽還五湯後,並不影響阿斯匹靈及其代謝物水楊酸之血中及腦中藥物濃度及相關藥物動力學參數。藥效學之出血時間結果顯示,空白組(完全無給予任何藥物)的出血時間為 100 ± 8.4 秒,而高劑量給予阿斯匹靈 (100 mg/kg)對照組的出血時間為 130 ± 11.7秒,實驗組(有給予補陽還五湯及阿斯匹靈)出血時間為 127 ± 1.15秒。而中劑量給予阿斯匹靈 (30mg/kg)對照組的出血時間為 147 ± 17.0 秒,實驗組(有給予補陽還五湯及阿斯匹靈)出血時間為 136 ± 7.02秒。比較之間的關係顯示,只有空白組與其他組(對照組及實驗組)之間具有統計上的差異 (P < 0.05)。出血時間 (Bleeding time)之藥效學測試結果顯示,給與大鼠補陽還五湯後,不影響血液之凝血功能。由本實驗之藥物動力學與藥效學之實驗結果,補陽還五湯與阿斯匹靈的使用,可能是可行的,實驗結果可提供臨床使用上做為參考。 |
英文摘要 | The proposed project is to evaluate the influence of bu-yang-huan-wu-tang on the pharmacokinetics of aspirin in rats. Aspirin is becoming a commonly prescribed pharmaceutical for the secondary prevention of ischemic stroke and transient ischemic attack (TIA) due to its apparent anti-coagulant effect. Bu Yang Huan Wu Tang (BTHWT) is a common formula consisting of traditional tonifying (Astralagus menbranaceus) and blood activating stasis resolving (Radix Angelicae sinensis, Radix Paeoniae rubra, Rhizoma Chuanxiong, Semen Persicae, and Phizoma Chuanziong) herbs for TIA and ischemic stroke prevention since the Qing dynasty in China. There is potential risk of hemorrhagic complications if aspirin is used as an adjunctive treatment with BYHWT. Therefore the herb-drug interaction of BYHWT and aspirin can be investigated using a well established pharmacokinetic animal model. In this work, we designed a parallel experiment with aspirin alone (10, 30 or 100 mg/kg, iv) and a group pretreated with bu-yang-huan-wu-tang (100 mg/kg, po), each for 5 consecutive days. On the sixth day we assessed the herb-drug pharmacokinetic interaction of free-form aspirin and salicylic acid by microdialysis. The validated microdialysis system consisted of two microdialysis probes, which were inserted into the right jugular vein toward right atrium and brain striatum of male Sprague-Dawley rats. The pharmacokinetic results indicate that the herbal formula of bu-yang-huan-wu-tang had no statistically significant affect on the pharmacokinetics of aspirin in blood and brain at the above dosage regimens, and the pharmacodynamic results indicated that bleeding time of the blank control group was 100 ± 8.4 sec. At the high dosage of aspirin (100 mg/kg), there were no significant differences between the aspirin alone group (130 ± 11.7 sec) and the experimental group (136 ± 7.02 sec). At the medium dosage of aspirin (30 mg/kg), there were also no statistically significant differences between the aspirin alone group (127 ± 1.15 sec) and the experimental group (147 ± 17.0 sec). But compared with the blank control group, bleeding time was prolonged significantly (P < 0.05) after the intravenous injection of aspirin (30, 100 mg/kg). Our study provides extremely constructive information for clinical practice to indicate when herbal formulation and aspirin can be used concurrently. |
本系統之摘要資訊系依該期刊論文摘要之資訊為主。