利福平对家兔静注安替比林药代动力的影响

选用健康家兔，分析利福平引起的静注安替比林药代动力学的改变，同时定量评估利福平对肝药酶活生的影响。提示，当药物消除符合一室模型时，可用该法计算有关的药代参数。     

利福平及异烟肼对家兔体内地西泮药代动力学的影响

用HPLC测定方法,研究了家兔多次ig利福平(100mg·kg^-1·d^-1×4)及异烟肼(50mg·kg^-1×4)后,对iv地西泮的药代动力学。结果表明,给药后利福平组肝微粒体细胞色素P-450含量增加98.1%,使地西泮的T_1/2β由98.77±19.38min减少到40.08±17.75min;AUC由143.52±41.41mg·min·L^-1减少到79.10±11.46mg·min·L^-1;CL由22.41±8.12ml·min^-1·kg^-1增加到43.96±10.38ml·kg^-1·min^-1。异烟肼组则表现出相反的作用。而利福平与异烟肼合用组对P-450含量及地西泮的动力学均无显著影响。提示利福平诱导家兔肝药酶的作用可加速地西泮的体内代谢过程,异烟肼抑制肝药酶减低地西泮的代谢。     

利福平注射液在结核病患者体内的药代动力学研究

测定利福平注射液的药代动力学。12例结核病患者静脉滴注300mg或600mg利福平注射液后,甲荧光偏振免疫法测定血药浓度。静脉给予利福平的平均血药峰浓度分别为(9.0±3.0)μg/mL和(17.5±5.0)μg/mL,机体清除率分别为(0.19±0.6)L/(kg h)和(0.14±0.03)L/(kg h),稳态分布容积为(0.66±0.14)L/kg和(0.64±0.1)L/kg。     

利福平、异烟肼及其联用时的临床药代动力学与应用

利福平、异烟肼均为临床治疗肺结核的一线药物。利福平抗菌谱广 ,对多种病原微生物均有抗菌活性 ,其中对生长缓慢或处于生长间歇期的结核菌有良好的抗菌作用 ,单独应用时 ,结核菌极易产生耐药性。异烟肼对结核菌有高度特异的抗菌作用 ,浓度较高时对增殖期结核菌有很强的杀菌作用 ,另外对细胞内结核菌也有杀灭作用 ,其作用比链霉素强５００倍 ,但结核菌对异烟肼也容易产生耐药性 ,而合用其它药物则可以明显地延缓或防止耐药菌株的出现。在结核病的化疗中 ,常将两药联合应用 ,不仅可以增强杀菌作用 ,还可以减少耐药菌株的产生。本文综述了利福…     

胸腺肽在家兔体内的药代动力学

目的研究家兔静注胸腺肽的药代动力学。方法用高效液相色谱法测定家兔血中胸腺肽浓度 ,3P87程序计算参数。结果与结论家兔静注胸腺肽后的药代动力学参数分别为 :Cmax=(30 .0 6± 9.2 7) μg/ml,t1/ 2 ( β) =(2 9.2 4± 2 3.78)min ,Ke =(0 .0 32 3± 0 .0 138)min-1,AUC0→∞ =(2 0 5 .6 3± 46 .48) μg·min/ml。     

双环醇对利福平和异烟肼在大鼠体内药代动力学的影响

目的：研究双环醇对利福平和异烟肼血药浓度及药代动力学参数的影响。方法：应用HPLC法测定与双环醇联用前后利福平和异烟肼的血药浓度,以DAS2．0药代动力学程序拟合药动学参数。结果：双环醇与利福平合用、双环醇与异烟肼合用、双环醇与利福平和异烟肼同时合用的各时间点中,除异烟肼6h的血药浓度三药合用组与其他组有显著性差异（P〈0．05）之外,其余时间点的血药浓度值在各组间均无显著性差异（P〉0．05）;药动学参数AUC（药时曲线下面积）（0-t）、AUC（0-∞）、MRT（体内平均驻留时间）（0-t）、MRT（0-∞）、t1/2x（半衰期）、tmax（达峰时间）、CLx/F（清除率）、Vx/F（表现分布容积）、Cmax（血药峰浓度）各组间均无显著性差异（P〉0．05）。结论：双环醇与利福平合用或与异烟肼合用,以及与利福平和异烟肼两药合用,均未见对利福平和异烟肼药动参数有明显影响。     

异烟肼对利福平的药动学影响

目的：研究异烟肼对利福平的体内药物动力学影响。方法：采用自身对照法2周期两制剂的交叉实验设计，比较了联合给药与单独给药的动力学参数。结果：异烟肼对利福平不存在药物间的不良交互影响。结论：为临床治疗安全有效地使用利福平和异烟肼提供实验依据。     

丙磺舒对阿莫西林在家兔体内的药动学影响

目的:观察丙磺舒对阿莫西林在健康家兔体内药动学的影响.方法:采用微生物杯碟法测定兔血清中阿莫西林的浓度.结果:阿莫西林单剂量肌内注射后,吸收迅速,Tmax=(0.78±0.09)h,Cmax=(0.87±0.30)μg·mL-1,其代谢模型为一级速率一房室模型.当阿莫西林和丙磺舒等剂量伍用时丙磺舒对阿莫西林药动学参数的影响达到最大值:阿莫西林的t1/2由(2.06±0.09)h延长至(5.50±0.52)h,AUC由(4.07±0.05)μg·mL-1·h增加至(13.75±3.09)μg·mL-1·h,Cmax由(0.87±0.30)μg·mL-1增加至(6.30±1.46)μg·mL-1,且三者统计学差异极显著(P<0.01).结论:丙磺舒对阿莫西林的药动学参数的影响呈S型,当两者等剂量伍用时影响最大.     

Influence of prednisolone on antipyrine elimination in patients with obstructive lung disease

Summary The influence of prednisolone on the elimination of antipyrine has been investigated. The one-sample antipyrine clearance was estimated in 23 outpatients with obstructive lung disease before and after treatment with prednisolone 30 or 50 mg/day for 7 days. During prednisolone administration antipyrine clearance decreased from 54.9±14.8 to 51.7±14.6 ml/min (mean±SD; p<0.05). The results indicate that prednisolone decreases the rate of antipyrine elimination, but not to an extent suggesting a clinically important change in hepatic drug metabolism.     

加替沙星对家兔茶碱药动学的影响

目的 :观察注射用加替沙星对茶碱在家兔体内药动学的影响。方法 :采用荧光偏振免疫分析法 (FPIA)测定氨茶碱单用及与加替沙星合用后家兔体内茶碱血清浓度 ,并对 2组药动学参数进行统计学处理。结果 :单用氨茶碱及与加替沙星合用后的药 -时曲线符合 -室模型。加替沙星使茶碱的AUC、血药浓度显著增加 (P均 <0 0 5 ) ;表观分布容积显著下降 (P <0 0 5 ) ;清除率显著下降 (P <0 0 1) ;消除半衰期相应延长 ,消除速率常数减少 ,但无统计学意义 (P >0 0 5 )。结论 :在家兔体内 ,合用加替沙星对茶碱的消除药动学有显著抑制作用     

甘草酸对小鼠安替比林及醋氨酚代谢的影响

目的研究甘草酸是否诱导小鼠肝细胞增殖及其对安替比林和醋氨酚代谢的影响。方法给小鼠甘草酸５０ｍｇ·ｋｇ－１或等量注射用水灌胃７ｄ后，比较两者间安替比林和醋氨酚有关药代动力学参数及肝ＤＮＡ含量和肝／体重比的差异。结果与对照组相比，甘草酸组小鼠安替比林Ｔ１２缩短４５３％，ＣＬ增加４３６％（Ｐ＜００５）；醋氨酚Ｔ１２延长５４６％，ＣＬ降低２９３％（Ｐ＜００５），尿液葡萄糖醛酸 醋氨酚含量减少１１８％（Ｐ＜００５）；肝ＤＮＡ含量及肝／体重比无明显改变。结论甘草酸能诱导小鼠安替比林代谢，抑制醋氨酚代谢，对肝细胞增殖无影响     

The effect of intravenous pretreatment with small liposomes on the pharmacokinetics and metabolism of antipyrine in rabbits.

The effect of intravenous pre-treatment with empty small liposomes on the pharmacokinetics and metabolism of antipyrine in rabbits has been investigated. The measured half-life of antipyrine was 104 min and the volume of distribution was 830 mL kg-1. The excretion of metabolites in a 24 h urine sample was measured, the main metabolite 4-hydroxyantipyrine was excreted to a level of 10% with the free drug accounting for 4%. The norantipyrine and 3-hydroxymethylantipyrine metabolites were excreted to a level of 8 and 7%, respectively. The intravenous administration of liposomes at a dose equivalent to 8 mg of egg yolk phosphatidylcholine daily for one week, had no significant effect on any of the measured pharmacokinetic parameters. The half-life after liposome treatment was 110 min and the volume of distribution was 790 mL kg-1, the metabolic pattern in the urine was also unaltered. The results suggest that the repeated administration of low doses of liposomes do not affect the pharmacokinetics and metabolism of antipyrine.     

Pharmacokinetic parameters of antipyrine in dog after hepatectomy

Pharmacokinetic studies with antipyrine were carried out on beagle dogs to determine the consequence of hepatectomy on hepatic drug metabolizing capacity, the rate of hepatic regeneration, and the possible beneficial effect of hepatocellular transplantation. The drug (250 mg) was administered by short IV infusion in three groups of dogs (first group, 65% hepatectomy; second group, 65% hepatectomy with hepatocyte transplantation; third group 80% hepatectomy). Pharmacokinetic parameters of antipyrine were evaluated before surgery and within 10 d after surgery. Blood samples were taken at frequent intervals after drug administration and antipyrine was assayed in plasma by a specific HPLC method with UV detection. Before surgery, the mean elimination half-life was about 1.1 h and total clearance averaged 6 L h^?1. In dogs with 65% hepatectomy, no statistical differences in pharmacokinetic parameters of antipyrine appeared before or after surgery. When 65% hepatectomy was associated with hepatocyte transplantation, a significant increase in elimination half-life and a significant decrease in total clearance were observed. The same statistical differences in the pharmacokinetic parameters were observed in the group with 80% hepatectomy. Transplantation of isolated hepatocytes into the spleen did not correct hepatocellular insufficiency. In this study, numerous laboratory tests were performed. A significant correlation was found between serum albumin, cholesterol, factor V, ALAT, total bilirubin, and ratio of aminoacids and the pharmacokinetic parameters of antipyrine.     

盐酸去氢骆驼蓬碱胶囊兔体内药物动力学及生物利用度研究

目的　研究盐酸去氢骆驼蓬碱胶囊在兔体内的药物动力学及其生物利用度。方法　采用反相高效液相色谱法测定家兔血浆药物浓度。结果　家兔灌胃给盐酸去氢骆驼蓬碱胶囊后血浆药物浓度在 4.73 h左右达峰值(1 .5 2 7mg· L-1) ,消除半衰期为 4.73 h,灌胃给胶囊剂的生物利用度为 1 7.1 4%。结论　家兔灌胃给盐酸去氢骆驼蓬碱吸收迅速 ,但生物利用度较低     

六味地黄丸对家兔体内格列齐特药动学的影响

目的研究六味地黄丸在家兔体内对格列齐特片代谢的影响。方法新西兰大白兔8只,每只予格列齐特80nag,po。经2周清洗期后,每只家兔予六味地黄丸每次8颗,po,tid,连续2周,第15天予相同剂量的格列齐特片。所有家兔均分别于给药前（0h）以及给予格列齐特片后不同时间点经耳缘静脉采血,HPLC法测定格列齐特的血浓度,DAS3．2．1计算药动学参数。结果格列齐特在家兔体内的药动学符合非房室模型。单用格列齐特家兔组,其tmax ρmax、AUC分别为（3．01±1．69）h、（51．91±8．38）mg·L^-1、（2551．08±15．58）mg·h·L^-1;联用六味地黄丸组,其tmax、ρmax、AUC分别为（1．04±1．06）h、（88．93±6．61）mg·L^-1、（1956．68±11．98）mg·h·L^-1。格列齐特在给予六味地黄丸前后的tmax、ρmax、AUC之间差异均有统计学意义（P〈0．05）。结论六味地黄丸对家兔体内格列齐特的药动学存在影响,可增加格列齐特的峰浓度,并且缩短其达峰时间。据此建议临床上两药合用时,应严密监测格列齐特浓度以及患者血糖值。     

甲磺酸酚妥拉明的血药浓度测定及其家兔体内的药动学

目的建立一种测定家兔血浆中甲磺酸酚妥拉明含量的方法,并应用于甲磺酸酚妥拉明溶液的药动学研究。方法家兔的给药方式采用溶液灌胃;血药浓度分析采用HPLC内标法。结果甲磺酸酚妥拉明血药浓度测定的线性关系为:y= 0.006 6ρ-0.013 3(r=0.999 7,n=3),线性范围为:5～250μg·L~(-1)。6只家兔药动学参数分别为:ρ_(max)(110.78±24.35)μg·L~(-1),t_(max)(11.67±2.58)min,k(0.46±0.13)h~(-1),t(1/2)(1.60±0.47)h,AUC_(0→6h)(104.50±15.13)μg·h·L~(-1),AUC_(0→∞)(119.12±19.10)μg·h·L~(-1)。结论我们建立的测定方法简便、灵敏、准确,可以用作甲磺酸酚妥拉明在家兔体内的药动学研究。