普拉西坦在动物体内的药物代谢动力学

为研究普拉西坦在犬和大鼠体内药代动力学规律,给犬灌服普拉西坦后,抽取不同时间的血液,分离血浆,用ＨＰＬＣ测定血浆中药物浓度,采用３ｐ８７ 程序计算药代参数;应用ＨＰＬＣ测定大鼠灌服普拉西坦后各组织和胆汁、尿、粪中药物浓度。结果显示：血药浓度－时间曲线符合一室开放模型,其体内的Ｔ１／２为２．３～３．９ 小时;大鼠灌服普拉西坦后３ 小时各组织中有较高的浓度,以肾脏为最高,肝脏次之,依序为肠、肺、肌、心、生殖腺、脾、脂肪;脑组织也能测到一定的量。２４小时从胆汁排泄原形药物占给药量的０．７％ ,７２小时从尿和粪中排出原形药物量分别占给药量的２８．２６％ 和６．３５％ 。用平衡透析法测定普拉西坦的血浆蛋白结合率约为２０．１％ ～２２．２％ 。以上结果表明,普拉西坦吸收快,分布广,消除也快。     

大剂量阿糖胞苷的临床药代动力学研究及毒副反应观察

应用反相高压液相色谱（ＨＰＬＣ）技术，研究８例急性髓细胞白血病（ＡＭＬ）缓解后使用大剂量阿糖胞苷（ＨＤＡｒａ－Ｃ）的临床药代动力学，发现用ＨＤＡｒａ－Ｃ３．０ｇ／次静滴２小时，药物在血浆中达到高峰浓度时间为９０分钟，峰浓度平均为５．５９μｇ／ｍｌ，滴注结束后迅速下降，４小时后降至０．１４μｇ／ｍｌ，ＡｒａＣ在体内以及双相清除，ｔ１／２α，ｔ１／２β平均分别为９．６分钟和１９２分钟，体内平均清除率４     

醋氯芬酸在大鼠体内的药代动力学

采用ＨＰＬＣ法研究醋氯芬酸在大鼠体内的药代动力学。醋氯芬酸在大鼠体内的吸收较为迅速，给药后约１０ｍｉｎ达到血药浓度峰值，其药－时曲线符合一级吸收的二室模型，分布半衰期仅为４ｍｉｎ左右，消除半衰期约为５０ｍｉｎ。三种剂量下的ＡＵＣ分别为４２．１、９０．３、１８１．８μｇｍｉｎ／ｍｌ，剂量与ＡＵＣ具有良好的线性关系，提示醋氯芬酸在大鼠体内的处置属于线性动力学，其动力学参数呈剂量非依赖性。大鼠按１０ｍｇ／ｋｇ剂量灌服醋氯芬酸后，心、胃、肠和肌肉组织内的浓度较高。醋氯芬酸在大鼠粪、尿和胆汁中的排泄较少。大鼠按１０ｍｇ／ｋｇ剂量灌服醋氯芬酸后，其２４ｈ内累积尿排泄百分率仅为０．０９０％±０．０１８％；其２４ｈ内累积粪便排泄百分率仅为０．２２％±０．０７％；其１２ｈ内累积胆汁排泄百分率仅为０．３３％±０．０９％。     

阿霉素脂质体犬肝动脉栓塞后阿霉素体内特征

目的：研究阿霉素脂质体－碘油犬肝动脉栓塞后的体内靶向性特征和药代动力学，方法：用高效液色相色谱法（ＨＰＬＣ）测定犬血浆和肝组织中阿霉素的浓度。结果：阿霉素脂质体－碘油栓塞组犬血浆阿霉素浓度显著低于阿霉素溶液灌注组（Ｐ〈０．０１）和阿霉素－碘油栓塞组（Ｐ〈０．０５），而其血浆阿霉素消除半衰期和肝组织中阿霉素中浓度与后两组比则显著增加（Ｐ〈０．０１，Ｐ〈０．０５）。结论：阿霉素脂质体与碘油混合肝动脉栓     

犬体内碳铂腹腔化疗药代动力学研究

应用高效液相色谱法（ＨＰＬＣ）对６只犬体内碳铂腹腔内给药药代动力学进行研究。碳铂３０ｍｇ／ｋｇ加生理盐水５００ｍｌ，快速腹腔给药，不同时间取腹腔液、门静脉及股静脉血测定总铂浓度。结果表明大剂量、大容量碳铂经腹腔给药后２４０ｍｉｎ内腹腔浓度最高，峰值浓度和平均浓度分别为股静脉浓度１３９倍和６４倍；门静脉次之，分别为股静脉浓度１３．３倍和６．５倍。碳铂腹腔给药在腹腔、门静脉和肝脏提供恒定持久的高药物浓     

口服去甲氧柔红霉素的药代动力学研究

目的 探讨国人使用口服４－去甲氧柔红霉素（ＩＤＡ）的药代动力学,力临床用药提供理论依据。方法 应用反向高压液相技术（ＨＰＬＣ）检测６例初发老年急性白血病患者口服ＩＤＡ后药物在血浆、单个核细胞和尿液中的药代动力学变化。结果 药物在单个核细胞内有较高的浓度,其变化与血浆内浓度变化一致;连续３ｄ用药,血浆及细胞内的浓度高峰出现于第２ｄ用药后的６０ｍｉｎ,或第３ｄ用药后的２ｈ左右;６ｄ后还能测出药物浓度。     

苦参碱的利尿作用及与药代动力学之间的关系

目的：研究苦参碱的利尿作用及作用时间与其药代动力学特征之间的相关性。方法：运用家兔尿管集尿法,观察灌服苦参碱后家兔尿量的变化。用HPLC法测定苦参碱在大鼠口服后的血浆浓度。结果：苦参碱90mg/kg灌服可显著地加家兔的尿量（P＜0．01）。最大效应出现在灌服的60min后,且维持时间可达灌服后的180min,大鼠口服后血浆药物达峰时间Tmax平均为55min,t1/2β平均为102min。结论：苦参碱对家兔有显著的利尿作用,其效应的维持相对滞后于药物在血浆中的衰减。     

固相萃取反向冲洗-反相HPLC法测定血浆中醋氯芬酸浓度

建立了反相ＨＰＬＣ法,测定血浆中醋氯芬酸的浓度,并对单剂量口服给药后的药代动力学进行了初步的探讨。血浆样本经大孔树脂小柱萃取后,以ＯＤＳ柱分析,流动相为甲醇水冰醋酸（６２∶３６∶２）,检测波长为２７５ｎｍ。在０．５１００μｇ／ｍＬ浓度范围内线性关系良好,最低检出限为０．３μｇ／ｍＬ。     

氟氧头孢在家兔体内的药代动力学和组织分布研究

目的：研究氟氧头孢在家兔体内的药代动力学和组织分布。方法：家兔单剂量静脉推注５０ ｍ ｇ／ｋｇ 氟氧头孢,采用ＨＰＬＣ法测定体液及组织中药物浓度。结果：静脉给药后血浆药－时曲线符合二室开放模型,氟氧头孢体内分布迅速,分布半衰期仅为０．０２３ ｈ,消除半衰期为０．２１３ ｈ, ＡＵＣ为（７９．９４±１３．３１） ｈ·μｇ／ｍ ｌ, 尿液、胆汁、肺、肾脏、卵巢及子宫中药物浓度较高。结论：氟氧头孢是一体内分布广、组织浓度高、消除半衰期短的头孢类抗生素     

依诺沙星对大鼠茶碱药代动力学的影响

为探讨国产依诺沙星（ＥＮＸ）大鼠血浆茶碱（ＴＰ）药动学的影响,给临床合理使用提供实验依据。经灌胃给予大鼠单剂量ＴＰ２０ｍｇ／ｋｇ,同时给予ＥＮＸ（３００ｍｇ／ｋｇ）３次,用ＨＰＬＣ法测定给ＴＰ后１、３、５、７、１２、２４小时的血浆ＴＰ浓度。结果显示茶碱以一室药动学模型消除,ＥＮＸ使浓度明显升高Ｔ１／２β延长,ＡＵＣ增大,血浆清除率下降,具有剂量依赖性,由此表明国产ＥＮＸ与ＴＰ有明确的相互作用,合用     

~3H-八厘麻毒素的分布和排泄

用~3H-八厘麻毒素注入小白鼠体内后,测定本药在血中的放射活性,其分布于胆囊最多,肝、肾次之,而以脑中最少,6小时后,已有52.4％由尿、粪中排出体外。本品与血浆蛋白的结合率,30分钟达60％。另外也测定了与肝、肾组织的结合率。     

肝肾移植术后他克莫司血药浓度影响因素的研究

目的：基于临床治疗过程的角度,研究影响他克莫司谷浓度的因素,为临床调整服药剂量提供参考。方法以肝肾移植术后患者为研究对象,服药后9～16小时测定血液中他克莫司谷浓度,分析谷浓度与可能的影响因素之间的关系。结果肾移植术后血药浓度高于肝移植术后,30～39岁年龄段血药浓度最高,女性血药浓度低于男性,服药剂量与血药浓度相关系数r分别为肝＝0．406,肾＝0．639。结论肝肾移植术后、性别、年龄、药物调整次数和服药剂量等都会影响他克莫司血药浓度。合并用药有利于控制血药浓度。服药剂量与谷浓度在一定范围内有相关。     

~3H-氧甲基山豆根碱的药物代谢动力学研究

本文报道~3H-氧甲基山豆根碱的药物代谢动力学。大白鼠一次灌胃给药后,血浆药物浓度对时问的曲线符合开放式二室模型。其主要参数是:t1/2_(Ka)=0.203hr t1/2_a=0.481hr,t1/2_β=9.429hr, K_(12)=0.582hr~(-1), K_(21)=0.799hr~(-1), K_(10)=0.132hr~(-1), T_(max)=0.61hr, C_(max)=0.461μg/m1。收集48小时内大白鼠的粪、尿测得排出的放射性分别为21.59%和1.97%     

荧光偏振免疫分析法在小分子药物小鼠血药浓度检测中的应用

目的：建立应用荧光偏振免疫分析法（FPIA）测定小鼠血药浓度的实验方法,探讨该方法测定庆大霉素、地高辛和丙戊酸钠3种常见小分子药物小鼠血药浓度的可行性。方法：选用庆大霉素、地高辛和丙戊酸钠标准品,采用荧光偏振（FP）值非线性拟合法确定药物检出限及线性范围,在线性范围内分别设置低、中和高3个浓度组,检测质控偏差、日间精密度和小鼠血清干扰水平。选用30只KM小鼠进行药物代谢曲线测试,分为庆大霉素组（肌肉注射5 μg·g^-1）、地高辛组（灌胃20 ng·g^-1）和丙戊酸钠组（灌胃15 μg·g^-1）,每组10只,给药后24 h内取5个时间点（1、3、6、12和24 h）测定小鼠血药浓度。结果：FPIA法检测3种药物的检出限均在50 μg·L^-1以下,线性范围较宽（大于10倍检出限）,检测质控误差小于5%,日间精密度较高[中和高浓度组变异系数（CV）<5%],小鼠血清对庆大霉素和地高辛的检测效果无明显影响[误差百分比（ER）<5%],高浓度血清对丙戊酸钠的检测效果有一定的负向影响（50%血清组ER为-12.84%）。小鼠给药1 h后庆大霉素达到血药浓度峰值,半消期3 h;1 h后地高辛达到血药浓度峰值,半消期>24 h;3 h后丙戊酸钠达到血药浓度峰值,半消期6~12 h。结论：FPIA法测定小分子药物小鼠血药浓度所需样本量小,精确度高,前处理简单,具有高通量和快速检测的优势特点,可广泛应用于药理学、药剂学和临床检测研究中。     

Disposition and pharmacodynamics of methamphetamine in pregnant sheep

To determine the placental transfer of methamphetamine, its subsequent fetal disposition, and its hemodynamic effects, we administered methamphetamine intravenously to 15 pregnant ewes 3 days after placement of maternal and fetal vascular catheters. Methamphetamine crossed the placenta within 30 seconds of its administration. Although the ewes had higher peak concentrations, the fetuses' longer elimination half-life ultimately led to higher fetal than maternal methamphetamine concentrations. The ratio of fetal tissue to plasma drug concentration 2 hours after administration was highest in the lung, followed by the placenta, kidney, intestine, liver, brain, and heart. Methamphetamine caused a 54% to 63% rise in maternal blood pressure, a 20% to 37% increase in fetal blood pressure, and a drop in fetal oxyhemoglobin saturation and arterial pH. We conclude that methamphetamine, in doses at or below what is commonly abused, has effects that could be detrimental to the health of the mother and her fetus.     

Chemoprophylaxis with oral amoxycillin against bacterial endocarditis: when should second doses be administered after dentistry?

The adequacy of serum bactericidal activity after oral amoxycillin given as prophylaxis against infective endocarditis was studied using a double blind randomised protocol in healthy volunteers having dentistry. One hour before their procedure 38 patients received 3 g amoxycillin syrup and 12 received matching placebo. Venous blood samples were drawn before and one and nine hours after dosing and serum amoxycillin concentrations determined using a standard bioassay. Samples containing amoxycillin had inhibitory titres measured against two reference isolates of viridans streptococci known to have caused infective endocarditis. The susceptibility to amoxycillin of one strain was high and the other low, respective minimal bactericidal and inhibitory concentrations being 0.08 and 0.04 mumol/l (0.03 and 0.015 microgram/ml) and 2.74 and 1.37 mumol/l (1 and 0.5 microgram/ml). Amoxycillin was detected in only post-treatment samples of patients given the active drug. There were no significant correlations between one or nine hour drug concentrations and age or physical characteristics, nor was there any relation to preceding food consumption. Correlations between drug concentrations at one and nine hours were weak (r = 0.34; p less than 0.05), but between corresponding drug concentrations and serum inhibitory titres there were consistent correlations (r = 0.46-0.48; p less than 0.005). Against the low susceptibility reference isolate bactericidal amoxycillin concentrations were encountered in only 20 of the 38 nine hour samples (95% confidence limits 34% and 66%). When repeat doses of amoxycillin are indicated after dentistry they should be given about four hours later, not eight hours later as commonly practised.     

GC-FID法同步测定人含服速效救心丸后血中冰片、川芎嗪含量

目的 探讨建立健康志愿者含服速效救心丸后吸收入血浆成分的药动学的研究方法，为临床治疗药物监测及证治药动学假说的研究提供实验依据。方法 建立GC—FID测定健康志愿者血浆中冰片、川芎嗪含量的方法，不同时间点取健康志愿者含服速效救心丸后的血浆并分别测定其冰片、川芎嗪浓度，经3P97软件处理数据得其药动学参数。结果 健康人血浆中线性范围为20～420ng／mL，线性关系良好，健康人含服速效救心丸后血浆中体内药时过程符合开放性一室模型，吸收、分布、排泄较为迅速。结论 所建立的GC—FID测定法灵敏、可靠，可较好地用于冰片、川芎嗪体内的药动学研究。     

Influence of cimetidine on pharmacokinetics of propranolol

Whole-blood propranolol concentrations were estimated for 12 hours after a single 80 mg oral dose was given in six patients taking cimetidine and two weeks after they had stopped the drug. Mean blood propranolol concentrations were higher throughout the sampling period when the patients were taking cimetidine than when they were not, and the difference was statistically significant between one and four hours (p less than 0.05). The mean relative bioavailability of propranolol, measured as the area under the concentration time curve, was significantly higher when the patients were taking cimetidine (p less than 0.025). The mean increase in bioavailability was 136.5 +/- 57.6%, and the results were consistent in each subject. It is concluded from these results that cimetidine reduces the hepatic first-pass extraction of propranolol.     

洛伐他汀在巴马香猪体内的分布和排泄

目的研究洛伐他汀在巴马香猪体内的分布和排泄特点。方法以抗动脉粥样硬化药物洛伐他汀为模型药,选择健康6月龄雄性巴马香猪为实验对象,经灌胃途径给药(45 mg/kg或2.4 mg/kg),采用RP-HPLC方法测定各组织及体液中的药物浓度,并对其分布和排泄过程进行研究。血浆蛋白结合率通过透析法测定。结果给药后,洛伐他汀快速分布到贲门、胃、小肠、肝、大肠、胰、前列腺、肺、肾、心、肌肉、睾丸、肾上腺、膀胱、脑和脾。以胃、肠、肝组织中药物浓度较高。单次给药4h后,贲门、胃、小肠、肝、心、肾上腺、膀胱药物浓度同给药后1h相比略有下降,其余组织均高于1 h。血浆蛋白结合率为95%以上,同正常人血浆非常一致。96 h尿中累积排泄量为给药量的7.4%,原形药经胆汁及粪排泄量达到80%以上。结论洛伐他汀在巴马香猪体内同人的分布排泄和血浆蛋白结合率相似,均在组织中广泛分布,血浆结合率达到95%以上,主要经胆汁和粪排泄。