中华烧伤杂志
中華燒傷雜誌
중화소상잡지
16
2010年
1期
37-40
,共4页
烧伤%二异丙酚%药代动力学%休克期%高代谢期
燒傷%二異丙酚%藥代動力學%休剋期%高代謝期
소상%이이병분%약대동역학%휴극기%고대사기
Burns%Propofol%Pharmacokinetics%Shock phase%Hypermetabolic phase
目的 了解严重烧伤家兔在休克期与高代谢期丙泊酚的药代动力学特征和差异.方法 将20只新西兰大白兔按随机数字表法分为烧伤组和假伤组,每组10只.将烧伤组家兔造成30%TBSA的Ⅲ度烫伤(以下称烧伤),伤后即刻复苏;6 h后静脉注射5.1 mg/kg丙泊酚,分别于注药后1、3、 5、 10、15、20、30、45、60、90 min于左侧颈外静脉取血1.5 mL;1周后重复上述注药及标本采集过程.假伤组家兔除致假伤外,其他处理同烧伤组.用高效液相色谱仪集中检测2组家兔血浆丙泊酚浓度,采用3P97实用药代动力学计算程序处理血浆药物浓度-时间数据,拟合药代动力学模型并求算参数. 结果 烧伤组家兔药物浓度-时间数据符合二房室模型,假伤组符合三房室模型.休克期,与假伤组家兔中央室分布容积[Vc,(3.1±1.5)L/kg]、曲线下面积[AUG,(25±7)mg·min·L~(-1)]、消除相半衰期[tl/2β,(113.4±93)min]、总清除率[CLs,(110±50)mL·kg~(-1)·min~(-1)]比较,烧伤组Vc[(8.8±4.2)L/kg]与AUC[(44±10)mg·min·L~(-1)]增大(t值分别为3.191与3.668,P值均小于0.01),tl/2β[(339±258)min]延长(t=2.932,P<0.05),CLs[(40±30)mL·kg~(-1)·min~(-1)]降低(t=-3.013,P<0.05).高代谢期,烧伤组家兔CLs[(180±40)mL·kg~(-1)·min~(-1)]显著高于假伤组[(90±30)mL·kg~(-1)·min~(-1),t=-3.013,P<0.05].与本组休克期比较,烧伤组家兔高代谢期Vc[(4.1±1.3)L/kg]与AUC[(24±5)mg·min·L~(-1)]显著减小(t值分别为2.979与3.766,P值均小于0.01),分布相半衰期[t1/2α,休克期为(16.1±13.1)min、高代谢期为(8.3±2.5)min]、t1/2β[(55±19)min]明显缩短(t值分别为9.065与8.795,P值均小于0.01),而CLs则显著增加(t=4.238,P<0.01). 结论 严重烧伤家兔休克期与高代谢期丙泊酚药代动力学差异较大,休克期以Vc、AUC增大,t1/2α、t1/2β延长,CLs降低为特点;高代谢期以CLs显著增加为特点.
目的 瞭解嚴重燒傷傢兔在休剋期與高代謝期丙泊酚的藥代動力學特徵和差異.方法 將20隻新西蘭大白兔按隨機數字錶法分為燒傷組和假傷組,每組10隻.將燒傷組傢兔造成30%TBSA的Ⅲ度燙傷(以下稱燒傷),傷後即刻複囌;6 h後靜脈註射5.1 mg/kg丙泊酚,分彆于註藥後1、3、 5、 10、15、20、30、45、60、90 min于左側頸外靜脈取血1.5 mL;1週後重複上述註藥及標本採集過程.假傷組傢兔除緻假傷外,其他處理同燒傷組.用高效液相色譜儀集中檢測2組傢兔血漿丙泊酚濃度,採用3P97實用藥代動力學計算程序處理血漿藥物濃度-時間數據,擬閤藥代動力學模型併求算參數. 結果 燒傷組傢兔藥物濃度-時間數據符閤二房室模型,假傷組符閤三房室模型.休剋期,與假傷組傢兔中央室分佈容積[Vc,(3.1±1.5)L/kg]、麯線下麵積[AUG,(25±7)mg·min·L~(-1)]、消除相半衰期[tl/2β,(113.4±93)min]、總清除率[CLs,(110±50)mL·kg~(-1)·min~(-1)]比較,燒傷組Vc[(8.8±4.2)L/kg]與AUC[(44±10)mg·min·L~(-1)]增大(t值分彆為3.191與3.668,P值均小于0.01),tl/2β[(339±258)min]延長(t=2.932,P<0.05),CLs[(40±30)mL·kg~(-1)·min~(-1)]降低(t=-3.013,P<0.05).高代謝期,燒傷組傢兔CLs[(180±40)mL·kg~(-1)·min~(-1)]顯著高于假傷組[(90±30)mL·kg~(-1)·min~(-1),t=-3.013,P<0.05].與本組休剋期比較,燒傷組傢兔高代謝期Vc[(4.1±1.3)L/kg]與AUC[(24±5)mg·min·L~(-1)]顯著減小(t值分彆為2.979與3.766,P值均小于0.01),分佈相半衰期[t1/2α,休剋期為(16.1±13.1)min、高代謝期為(8.3±2.5)min]、t1/2β[(55±19)min]明顯縮短(t值分彆為9.065與8.795,P值均小于0.01),而CLs則顯著增加(t=4.238,P<0.01). 結論 嚴重燒傷傢兔休剋期與高代謝期丙泊酚藥代動力學差異較大,休剋期以Vc、AUC增大,t1/2α、t1/2β延長,CLs降低為特點;高代謝期以CLs顯著增加為特點.
목적 료해엄중소상가토재휴극기여고대사기병박분적약대동역학특정화차이.방법 장20지신서란대백토안수궤수자표법분위소상조화가상조,매조10지.장소상조가토조성30%TBSA적Ⅲ도탕상(이하칭소상),상후즉각복소;6 h후정맥주사5.1 mg/kg병박분,분별우주약후1、3、 5、 10、15、20、30、45、60、90 min우좌측경외정맥취혈1.5 mL;1주후중복상술주약급표본채집과정.가상조가토제치가상외,기타처리동소상조.용고효액상색보의집중검측2조가토혈장병박분농도,채용3P97실용약대동역학계산정서처리혈장약물농도-시간수거,의합약대동역학모형병구산삼수. 결과 소상조가토약물농도-시간수거부합이방실모형,가상조부합삼방실모형.휴극기,여가상조가토중앙실분포용적[Vc,(3.1±1.5)L/kg]、곡선하면적[AUG,(25±7)mg·min·L~(-1)]、소제상반쇠기[tl/2β,(113.4±93)min]、총청제솔[CLs,(110±50)mL·kg~(-1)·min~(-1)]비교,소상조Vc[(8.8±4.2)L/kg]여AUC[(44±10)mg·min·L~(-1)]증대(t치분별위3.191여3.668,P치균소우0.01),tl/2β[(339±258)min]연장(t=2.932,P<0.05),CLs[(40±30)mL·kg~(-1)·min~(-1)]강저(t=-3.013,P<0.05).고대사기,소상조가토CLs[(180±40)mL·kg~(-1)·min~(-1)]현저고우가상조[(90±30)mL·kg~(-1)·min~(-1),t=-3.013,P<0.05].여본조휴극기비교,소상조가토고대사기Vc[(4.1±1.3)L/kg]여AUC[(24±5)mg·min·L~(-1)]현저감소(t치분별위2.979여3.766,P치균소우0.01),분포상반쇠기[t1/2α,휴극기위(16.1±13.1)min、고대사기위(8.3±2.5)min]、t1/2β[(55±19)min]명현축단(t치분별위9.065여8.795,P치균소우0.01),이CLs칙현저증가(t=4.238,P<0.01). 결론 엄중소상가토휴극기여고대사기병박분약대동역학차이교대,휴극기이Vc、AUC증대,t1/2α、t1/2β연장,CLs강저위특점;고대사기이CLs현저증가위특점.
Objective To investigate the characteristics and differences of propofol pharmaookinet-ics in shock phase and hypermetabolie phase in severe burn in rabbits. Methods Twenty New Zealand rabbits were assigned to burn group (n=10) and sham injury group (n=10) according to the random number table. Rabbits in burn group were inflicted with 30% TBSA full-thickness scald (named burn be-low), resuscitated instantly, and were intravenously injected with 5.1 mg/kg propofol 6 hours after injury.1.5 mL blood was collected from left external jugular vein at 1,3, 5, 10, 15, 20, 30, 45, 60, 90 minute (s) after injection respectively. Above procedure was performed again 1 week later. Rabbits in sham injury group were treated similarily as rabbits in burn group but were sham scalded. Propofol concentration in plas-ma was determined with high performance liquid chromatography. Data of propofol concentration-time were analyzed with 3P97 practical pharmacokinetics calculating program, and then the most fit compartment model was selected to calculate pharmacokinetic parameters. Results The blood concentration-time curve of propofol fitted in with the two-compartment model in burn group, and three-compartment model in sham inju-ry group. During shock phase, comparing with central compartment distribution volume [Vc, (3.1±1.5) L/kg], area under curve [AUC, (25±7) mg·min~(-1)·L~(-1)], elimination phase half life [t1/2β, (113±93)min], clearance [CLs, (110±50) mL·kg~(-1)·min~(-1)] of rabbits in sham injury group, Vc[(8.8±4.2) L·kg~(-1)] and AUC [(44±10) mg·min·L~(-1)] increased significantly (with t value respectively 3.191 and 3.668, and Pvalues both below 0.01); t1/2β[(339±258) min] prolonged (t=2.932, P <0.05); CLs [(40±30) mL·kg~(-1)·min~(-1)] decreased (t=-3.013, P <0.05) in burn group. During hypermetabolic phase, CLs[(180±40) mL·kg~(-1)·min~(-1)] of rabbits in burn group was significantly high-er than that in sham injury group [(90±30) mL·kg~(-1)·min~(-1), t=-3.013, P<0.05]. Comparing with those of rabbits in burn group during shock phase, Vc [(4.1±1.3) L/g] and AUC [(24±5) mg·min·L~(-1)] decreased significantly (with t value respectively 2.979 and 3.766, and P value both below 0.01) ; distribution phase half time [t1/2α, shock phase (16.1±13.1) min and hypermetabolic phase (8.3±2.5) mini and t1/2β[(55±19) mini shortened obviously (with t value respectively 9.065 and 8.795,and P values both below 0.01) ; CLs increased significantly (t =4.238, P < 0.01) during hypermetabolic phase. Conclusions There are great differences in propofol pharmacokinetics between shock phase and hypermetabolic phase in severely burned rabbits. The change is characterized by increase in Vc and AUC,extension of t1/2α and t1/2β, decrease in CLs during shock phase and obvious increase of CLs during hy-permetabolic phase.
