卡鉑-PECE水凝膠大鼠腹腔藥物代謝動(dòng)力學(xué)研究
發(fā)布時(shí)間:2018-03-15 10:21
本文選題:卡鉑 切入點(diǎn):PECE水凝膠 出處:《遵義醫(yī)學(xué)院》2014年碩士論文 論文類(lèi)型:學(xué)位論文
【摘要】:目的:將載有卡鉑的PECE水凝膠藥物緩釋系統(tǒng)注入到大鼠腹腔,通過(guò)反向高效液相色譜法來(lái)測(cè)定不同時(shí)間段的大鼠血漿中卡鉑的濃度,分析其藥物代謝動(dòng)力學(xué)特點(diǎn),旨在為卡鉑-PECE水凝膠緩釋系統(tǒng)腹腔化療提供理論依據(jù)。 方法:首先制備卡鉑-PECE水凝膠,將18只雌性健康的Wistar大鼠隨機(jī)分為生理鹽水組、卡鉑組、卡鉑-PECE水凝膠組,通過(guò)反向高效液相色譜法來(lái)測(cè)定各組給藥后10min、30min、1h、2h、3h及4h大鼠血漿中卡鉑濃度,并分析其藥物代謝動(dòng)力學(xué)特點(diǎn),并比較各種給藥方式的毒副作用。 結(jié)果:卡鉑-PECE水凝膠在低溫時(shí)呈可以注射的溶膠態(tài),在37℃時(shí)呈不流動(dòng)的凝膠態(tài);將卡鉑溶液注入到大鼠腹腔后,測(cè)定10min、30min、1h、2h、3h及4h卡鉑組的血漿藥物濃度分別為:0.883±0.0036mg/ml、0.982±0.0051mg/ml、0.499±0.0046mg/ml、0.125±0.0002mg/ml、0.031±0.0006mg/ml、0.007±0.000005mg/ml。卡鉑-PECE水凝膠組在相同時(shí)間點(diǎn)的藥物濃度分別為:0.720±0.0003mg/ml、0.810±0.0023mg/ml、0.615±0.0034mg/ml、0.151±0.0023mg/ml、0.037±0.0002mg/ml、0.0090±0000006mg/ml。比較兩組數(shù)據(jù),差異有統(tǒng)計(jì)學(xué)意義(P0.05)?ㄣK時(shí)間曲線下面積約為1.0940±0.002,卡鉑-PECE水凝膠組時(shí)間曲線下面積約為1.1116±0.003,比較兩組數(shù)據(jù),差異有統(tǒng)計(jì)學(xué)意義(P0.05)。對(duì)大鼠重要臟器而言,PECE水凝膠并未增強(qiáng)卡鉑的毒副作用。 結(jié)論:作為一種可以注射的藥物緩釋系統(tǒng),PECE水凝膠具有良好的藥物緩釋特性,,可以將所裝載的抗癌藥物-卡鉑緩慢地釋放到大鼠腹腔進(jìn)而吸收入血并較長(zhǎng)時(shí)間維持較高濃度,為卡鉑-PECE水凝膠腹腔化療奠定理論基礎(chǔ)。
[Abstract]:Objective: to inject the PECE hydrogel drug delivery system carrying carboplatin into the abdominal cavity of rats, and to determine the concentration of carboplatin in rat plasma at different time intervals by reverse performance liquid chromatography (RHPLC), and to analyze the pharmacokinetic characteristics of carboplatin. To provide theoretical basis for intraperitoneal chemotherapy of carboplatin-PECE hydrogel sustained release system. Methods: carboplatin PECE hydrogels were prepared. Eighteen female healthy Wistar rats were randomly divided into normal saline group, carboplatin group and carboplatin-PECE hydrogel group. The plasma levels of carboplatin were determined by reverse high performance liquid chromatography (RHPLC) in rats at 10 min, 30 min, 1 h, 2 h and 4 h after administration. The pharmacokinetic characteristics of carboplatin were analyzed, and the toxicity and side effects of various drug administration methods were compared. Results: carboplatin-PECE hydrogels showed injectable sol at low temperature and unflowing gel at 37 鈩
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