Ceftazidime的犬组织浓度及药代动力学研究

用6条健康犬进行了Ceftazidime的药代动力学研究及组织浓度测定。所有试验犬均静脉及肌肉交叉注射本品20mg/kg。药物血清浓度及组织浓度测定采用微生物杯碟法。 实验结果显示静脉及肌注后的血清药物浓度-时间曲线分别符合二室及一室开放模型。静注后即刻的平均血药浓度为167.28±15.73μg/ml,肌注0.75小时后的峰浓度为54.86±11.42μg/ml, 静注及肌注后的消除相半衰期分别为1.61小时和1.44小时,表观分布容积各为0.35L/kg和0.34L/kg。 静注及肌注Ceftazidime 20mg/kg 1小时后的组织浓度测定结果表明肾脏浓度最高,达189.03±79.38μg/ml(im)和257.04±59.19μg/ml(iv),其次是胆汁浓度。其他脏器组织浓度依下列次序减低:子宫、前列腺、肝、肺、小肠、胰腺、肌肉、心和脾。脑组织浓度最低,其值为0.31±0.lμg/ml(im)和0.77±0.09μg/ml(iv)。     

芍药甙的药代动力学研究

芍药是白芍的主要成份,狗iv芍药甙11.25mg/kg后,血药浓度曲线符合二室模型。动力学参数:T_(1/2)(α)为6.29±1.80min,T_(1/2)(β)为133.41±84.89min,VB为0.54±0.10L/kg,CL为3.41±1.01ml/kg·min~(-1)。本品静注后迅速以原型出现于尿中,前20min和7h尿中累积排泄量占静注量分别为36.85%和79.33%,7h胆汁中累积排泄量占静注量为3.77%     

环丙沙星在老年慢性阻塞性肺病患者多次给药的药动学研究

应用微生物法测定6名老年慢性阻塞性肺病患者多次po环丙沙星片后的血清药物浓度,药物体内过程符合一室模型,其主要药动学参数分别为:T_(1/2)=5.14±1.13h,Vc/F=6.6±4.2L╱kg,(C∞)max=2.73±1.02μg/ml;T_p~′=0.96±0.44h,测定方法平均回收率为101.6％。     

氧氟沙星药物动力学和体外抗菌活性

6名受试者口服氧氟沙星400mg后,药-时曲线符合一室开放模型。T_(max)和C_(max)分别为1.3h和4.4μg/mL,T_((1/2)ka),T_((1/2)ke)分别为0.8和3.7h,C1为0.36L/(h·kg),V_d为1.9 L/kg。该药对革兰阳性或阴性细菌均有高度抗菌活性,对变形杆菌、痢疚杆菌、大肠杆菌、枸橼酸杆菌、伤寒杆菌和金葡菌等的抑菌率均>90％。     

TEMOCILLIN在犬体内的药代动力学及组织浓度

Temocillin的犬药代动力学及组织浓度研究是用微生物法测定血清及组织中药物浓度。静注和肌注本品20mg/kg后,体内药物转运过程分别符合开放型二室和一室模型。静注本品后即刻血浓度为141.1± 38.4μg/ml,分布相半衰期仅为0.06小时,故可迅速达到有效杀菌浓度。肌注后0.49小时达峰值,为47.8μg/ml。肌注与静注后血浆清除半衰期分别为1.23 ±0.14和1.08±0.13小时。总表观分布容积分别为0.29±0.01和0.26±0.05L/kg。生物利用度为93.1％。 4只犬分别单次静脉注射本品20gm/kg,测定1小时后各组织浓度。结果显示,胆汁中药物浓度高达176.7±123.4μg/ml, 为血清浓度的5倍,其次肝组织浓度为43.45±9.91μm/ml,略高于血浓度。按浓度递减顺序,其它组织分别为骨骼肌、肺、子宫、肾、胰腺、前列腺、脾、小肠和心肌。脑组织和脑脊液药物浓度未测出。     

对乙酰氨基酚咀嚼片相对生物利用度测定

2名健康受试者一次po两种对乙酰氨基酚咀嚼片后,用高效液相法测定ab的血药浓度。其血药农度和过程符合一室模型。国产对乙酰氨基酚咀嚼片A(tempra A)的药代动力学为:T1/2Ka=0.3806±0.2816h,T_(1/2)K_e=1.761±0.8930h,T_(max)=0.9023±0.4179h,C_(max)=7.0728±1.2264mg/L AUC=26.8579±10.7680μg·ml~(-1)·h~(-1)。tempra B的药代动力学为:T_(1╱2)Ka=0.2993±0.2584h,T_(1╱2)Ke=1.9720±0.470h,T_(max)=0.8322±0.5263h,C_(max)=6.7487±2.1925mg/L,AUC=25.0871±5.7059μg·m1~(-1)·h~(-1),国产对乙酰氨基酚痛咀嚼片与进口对乙酰氨基酚咀嚼片B(tempra B)的相对生物利用度为107.06％。提示两种对乙酰氨基酚咀嚼片的生物利用度相仿。     

大剂量奈替米星在新生儿体内的稳态药物动力学及临床疗效

目的:研究iv gtt奈替米星在新生儿体内的稳态药物动力学,观察疗效和安全性.方法:7例新生儿患者按7mg/kg.qd,iv gtt奈替米星,用药3d后用荧光偏振免疫法测定血药浓度,同时对奈替米星的抗感染效果及不良反应进行观察.结果:新生儿iv gtt奈替米星后,呈二房室动力学模型,主要药动学参数:C_(max)(18.38±5.43)μg/ml,T_(1/2β)(5.21±1.14)h.Vc(0.34±0.10)L/kg,CL(0.25±0.05)L/h,AUC(81.67±16.00)[(mg/L)·h]用药7d临床疗效满意并未发现不良反应.结论:肾功能正常的新生儿奈替米星qd iv gtt可获得较好的疗效并具有良好的安全性.     

氧氟沙星三种给药途径的药物动力学(英文)

本文报道42例呼吸道感染病人用inf,im和po三种途径给氧氟沙星后的药物动力学特性。血药浓度经3P87程序拟合,inf和im药物动力学模型符合二房室,po为一房室。inf,im,po后氧氟沙星的主要药物动力学参数为:T_2~1β6.0±1.3,5.0±1.0和T_2~1K5.0±0.7h;V_c58±16,68±27和V_d94±25l;C_(max)3.9±1.0,2.8±0.9和1.9±0.7μg·ml~(-1);Cl 13±4,14±4和14±3L·h~(-1)。     

ELISA法研究新型重组人肿瘤坏死因子在小鼠体内的药代动力学

目的研究新型重组人肿瘤坏死因子(nrhTNFα)在小鼠体内的药代动力学。方法给小鼠分别im和ivnrhTNFα后,按不同时间点采血,分离血清,采用双抗体夹心ELISA法测定血清中nrhTNFα的浓度,用DAS药动学软件进行曲线拟合并计算参数。结果nrhTNFα5.51μg·kg-1、24.60μg·kg-1小鼠im后药动学特征符合一室开放模型,呈一级动力学消除。nrhTNFαim给药能迅速吸收入血,Tmax分别为0.17h和0.33h。T1/2分别为1.25h和0.73h,AUC随剂量增加而成比例增加。nrhTNFα5.51μg·kg-1小鼠iv后符合二室开放模型,呈一级动力学消除,T1/2β为0.37h,AUC为771.24ng·L-1·h-1。结论nrhTNFαim和iv的药动学行为在小鼠体内分别符合一室和二室开放模型,均呈一级动力学消除。im给药的生物利用度为48.84%,可考虑作为替代iv的一种安全给药途径。     

吡喹酮不同途径给药在大鼠体内药代动力学及自胆汁中的排泄

大鼠iv吡喹酮20mg/kg,血药浓度时间曲线符合二室开放模型。消除快,t1/2β=0.36±(SD)0.07h。im10,20,40mg/kg或ig100mg/kg后,血药浓度达峰时间较快,但消除相与iv比却相对明显缓慢。MAT_(im)和MAT_(ig)均大于MRT_(ivo)ig的生物利用度为13.2%,有明显首过效应。im则吸收完全,当im10和20mg/kg时消除动力学呈线性关系,而当增至40gg/kg时,有呈非线性趋势。大鼠在im20mg/kg,iv20mg/kg以及ig300mg/kg后,胆汁中均能检测出原形吡喹酮,其浓度以iv最高,im居中,ig最低。     

用HPLC法测定大鼠血浆和胆汁中芹菜素的浓度

目的：建立HPLC法测定静脉给药后大鼠体内的芹菜素浓度。方法：采用HPLC法,色谱柱为Dikma C18柱,流动相为甲醇：0．2％（V／V）磷酸水溶液-66．5：33．5,检测波长350nm。用该方法测定5只大鼠静脉给药后不同时间点的血浆及胆汁中芹菜素浓度,计算主要药动学参数及胆汁排泄率。结果：血浆药物浓度的标准曲线在0．04～8μg／mL范围内线性关系良好（r=0．9998）,胆汁药物浓度标准曲线在0．25～8μg／mL范围内线性关系良好（r=0．9998）,血浆和胆汁的精密度和方法回收率均良好。芹菜素静脉给药后符合二室模型,消除半衰期为95．2min,胆汁排泄率为5．64％。结论：该方法灵敏、快速、准确,能够用于芹菜素的药动学研究。芹菜素静脉给药后,血浆浓度迅速下降,部分通过胆汁排泄。     

Multiple-dose pharmacokinetics of piperacillin and azlocillin in 12 healthy volunteers

The pharmacokinetic profile of piperacillin and azlocillin after multiple-dose administration to healthy volunteers was studied. Twelve healthy volunteers received either piperacillin 4 g (as the sodium salt) or azlocillin 4 g (as the sodium salt) as a 20-minute infusion every six hours for five doses. After a one-week washout period, subjects received identical treatment with the alternate drug. Serum and urine concentrations of piperacillin and azlocillin were measured using a reversed-phase high-performance liquid chromatographic assay, and the pharmacokinetic analysis of serum concentration-versus-time data was performed using a computerized program. A standard open-model equation for i.v. infusions was used. Mean serum concentrations of piperacillin and azlocillin after dose 5 were 344 +/- 66 micrograms/mL and 414 +/- 86 micrograms/mL, respectively. The terminal elimination half-life of azlocillin (1.1 +/- 0.2 hr) was significantly longer than that of piperacillin (0.75 +/- 0.13 hr) (p less than 0.05). Total body clearance of azlocillin (125 +/- 25 mL/min) was significantly less than that of piperacillin (226 +/- 43 mL/min) after dose 5. Azlocillin showed accumulation between the first and fifth doses. Twelve hours after administration of dose 5, 75% of azlocillin and 57% of piperacillin were excreted unchanged into the urine. In healthy volunteers, azlocillin produced higher and more prolonged serum concentrations than piperacillin after administration of equivalent i.v. doses. Further studies are needed to determine the clinical importance of these observations.     

Pharmacokinetics of sulpiride in humans after intravenous and intramuscular administrations.

The pharmacokinetics of sulpiride in plasma, red blood cells (RBC), and urine were investigated after administration of 100 mg by the iv route to 15 subjects and by the im route to 12 subjects. The concentrations of sulpiride in plasma, RBC, and urine were measured by HPLC. All the data were consistent with a two-compartment, open-body model. After iv administration, the mean +/- SD apparent elimination half-life of sulpiride was 6.47 +/- 1.00 h, and the mean +/- SD volume of distribution at steady state was 0.94 +/- 0.23 L/kg. Renal clearance (119.5 +/- 28.2 mL/min) was very close to total clearance (127.8 +/- 26.2 mL/min). In urine, the mean +/- SD recovery in form of the unchanged drug was 90.0 +/- 9.68% of the administered dose, and the excretion rate versus time showed an elimination half-life similar to that found in plasma. The values of all these parameters were very close to those obtained after im administration. The sulpiride partition coefficient between RBC and plasma did not show any significant change as a function of time and concentration, with a mean value +/- SD of 1.00 +/- 0.043, indicating that sulpiride is evenly distributed between RBC and plasma. The pharmacokinetic parameters determined from the plasma and the RBC data were similar.     

Pharmacokinetics and bioavailability of a new formulation of teicoplanin following intravenous and intramuscular administration to humans.

Pharmacokinetics, bioavailability, and local tolerance (at the site of intramuscular administration) of a new formulation of teicoplanin (400 mg/3 mL) were investigated in 24 normal, healthy, male volunteers. A single dose of 6 mg/kg was administered intravenously and intramuscularly using a randomized crossover design. Volunteers and investigator were blinded as to the route of administration; placebo was administered by the other route. Blood and urine samples were collected for 21 days and were analyzed for microbiological activity. The median (range) pharmacokinetic parameters of teicoplanin following single-dose iv administration were as follows: steady-state volume of distribution of 1.6 (1.2-2.8) L/kg; total clearance of 10.2 (8.6-15.1) mL/h/kg; renal clearance of 10.0 (7.9-13.8) mL/h/kg; and terminal disposition half-life of 168 (111-278) h. Following single-dose im administration, significantly more subjects complained of pain following administration of teicoplanin (58%) compared with placebo (4%). Teicoplanin was completely absorbed with a median (range) peak serum concentration of 12.3 (6.6-37.5) micrograms/mL occurring at a median (range) time of 4.1 (0.7-6.1) h. Since the 90% confidence interval for the ratio of areas under the serum concentration-time curve falls within the range of 80 to 120%, the extent of systemic absorption of teicoplanin following im administration is equivalent to that following iv administration.     

Delivery and Biodistribution of Traceable Polymeric Micellar Diclofenac in the Rat

The nonsteroidal anti-inflammatory drugs elevate cardiovascular risk, perhaps, due to their accumulation in the heart and kidneys. We designed nanodelivery systems for cardiotoxic diclofenac to reduce its presence in these organs. Diclofenac ethyl ester (DFEE) was encapsulated in traceable micelles based on poly(ethylene oxide)-b-poly(ε-caprolactone) (DFEE-PCL-TM) or poly(ethylene oxide)-b-poly(α-benzyl carboxylate-ε-caprolactone) (DFEE-PBCL-TM). Diclofenac pharmacokinetics and tissue distribution were studied after intravenous (iv) and intraperitoneal administration of the nanoformulations and compared with those after iv doses of free diclofenac (n = 3-6/group). The average diameters for DFEE-PBCL-TM and DFEE-PCL-TM were 37.2 ± 0.06 and 45.1 ± 0.06 nm, respectively. Drug concentration dropped below the assay sensitivity after free drug administration in 6 h, but persisted for 24 h following DFEE-PBCL-TM (2.3 ± 1.4 μg/mL) and DFEE-PCL-TM (1.9 ± 0.6 μg/mL) iv administration. The diclofenac heart:blood and kidney:blood ratios were 5- to 12-fold lower with the nanoformulations than with free diclofenac. Near-infrared fluorescence measurements in tissues suggested exposure patterns to nanocarriers parallel with those achieved for delivered diclofenac by nanoformulations. Administration of DFEE-PCL-TM by iv or intraperitoneal injection, resulted in comparable pharmacokinetics and 6 h postdose near-infrared fluorescence in the heart, kidneys, liver, and spleen. When compared to each other, DFEE-PBCL-TM showed significantly lower diclofenac levels in the heart compared to DFEE-PCL-TM (0.3 ± 0.03 vs. 0.5 ± 0.1 μg/g). Developed nanoformulations of diclofenac prolonged diclofenac circulation and reduced its presence in the heart and kidneys, strongly suggesting cardiac-safe delivery vehicles for diclofenac.     

1,6-二磷酸果糖镁在大鼠体内的药动学研究

目的研究大鼠静脉注射不同剂量 1,6 二磷酸果糖镁 (FDP Mg)后的药动学。方法大鼠 2 0只随机分成 2组 ,分别静脉注射FDP Mg 10 0、2 0 0mg/kg ,在设定的时间点采血 ,测定血清中的FDP及Mg2 + 浓度 ,DAS程序计算药动学参数。结果大鼠静脉注射FDP Mg后 ,Mg2 + 血药浓度 时间曲线符合二室开放模型。其t1/2α为 0 .12～ 0 .14h ,t1/2 β为 1.78～ 1.89h ,分布容积 (V)为 3.2 6～ 4 .5 7L/kg ,显示非剂量依赖性特征。FDP在血清中代谢迅速 ,消除半衰期t1/2el为 0 .0 5 7～ 0 .0 86h ,平均滞留时间 (MRT)为 0 .0 90～ 0 .12 4h ,血浆清除率 (Cl)为 3.4 8～ 3.77L/ (kg·h)。结论FDP和Mg2 + 的药动学特征差异明显 ,表明FDP Mg在体内解离成FDP和Mg2 + 两部分后按照各自的代谢特征从体内消除。     

Pharmacokinetics of recombinant human granulocyte colony-stimulating factor in the rat. Single and multiple dosing studies.

The pharmacokinetics of recombinant human granulocyte colony-stimulating factor (rhG-CSF) were investigated in male Sprague-Dawley rats at a dose of 5 micrograms/kg. The serum concentrations of rhG-CSF were monitored using a specific sandwich enzyme immunoassay. In single-dose studies, the influence of routes of administration were evaluated. For iv administration, the serum concentration-time data showed the rapid disappearance of rhG-CSF from the systemic blood and a mean residence time (MRT) of 1.341 hr. For sc, im, and ip administration, lower peak serum levels were observed, but after 2 to 3 hr, rhG-CSF levels were higher than those for iv administration. The MRTs after sc, im, and ip injections were 3.918, 2.894, and 3.538 hr, respectively. The serum concentration profiles after extravascular injections showed that an im injection gave slightly faster absorption kinetics of rhG-CSF from the injection site into systemic blood than did sc and ip injections. In multiple-dose studies, rhG-CSF was injected into animals iv and sc at 5 micrograms/kg/day for 7 days. On the day 7 the serum concentration-time profiles after rhG-CSF administration were compared between single and multiple dosing. The AUC after iv multiple dosing decreased by 17.4%, although half-lives and the volume of distribution were not significantly different between single and multiple dosing groups. The AUC after sc multiple dosing decreased by 25.6%; however, the bioavailability and observed maximum serum concentration of rhG-CSF were not significantly different. These results showed that the clearance of rhG-CSF increased after multiple dosing, although the mechanism of increased clearance was not apparent.     

Pharmacokinetics of azelastine and its active metabolite, desmethylazelastine, in guinea pigs.

Pharmacokinetics of azelastine (AZ) and its major active metabolite desmethylazelastine (DAZ) after iv or po administration of 1 mg/kg [14C]AZ hydrochloride or unlabeled AZ hydrochloride were studied in guinea pigs. Total 14C radioactivity concentrations in blood, plasma, lung, urine, and feces were determined by liquid scintillation counting. AZ and DAZ concentrations in the plasma and lung samples were determined by HPLC methods. For pharmacokinetic modeling, the mean concentrations of AZ and DAZ in plasma were converted to those in blood. Following the iv or po dose, AZ blood concentrations declined biexponentially with the distribution and elimination phases. The open two- and one-compartment models for AZ and DAZ concentrations in blood, respectively, and the open one-compartment model for the two compounds in lung tissue describe the experimental data reasonably well. The apparent volume of distribution of AZ suggested that the drug was widely distributed in the body. The mean lung/blood concentration ratios, which varied from 14.2 to 20.1 in the iv- and po-dosed animals for AZ and from 96.7 to 140.3 in the iv- and po-dosed groups for DAZ, respectively, indicate the capacity of the lung ("target tissue") for preferential uptake of the drug and its active metabolite. The efficiency of the desmethyl metabolite uptake into the lung was about 6-fold greater than that of AZ. The clearance of AZ from the body was faster than that of DAZ following either po or iv administration. The estimated availability of the AZ oral dose in guinea pigs was 0.19, which suggested that AZ was subjected to an extensive hepatic first-pass metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)