恩诺沙星在眼斑拟石首鱼体内的药物代谢动力学

应用反相高效液相色谱法 (RP- HPL C)研究了恩诺沙星在眼斑拟石首鱼 (Sciaenops ocellatus)体内的药物代谢动力学。实验数据经 DAS药代动力学分析软件分析后得出 :腹腔注射组血浆的药时数据符合一级吸收二室模型 ,动力学方程为 :C =4 .92 5 e- 1 .4 52 t +2 .730 e- 0 .0 75t ,其主要药代动力学参数 :AU C37.5 33mg· L- 1· h、Cmax 4 .74 7mg/ L、Tmax0 .75 0 h、t α0 .4 77h、t β9.2 92 h、Vd/ F 1 .6 76 L / kg、t Ka0 .1 70 h、Ka 4 .0 81 / h、K 6 .71 4 / h、K1 0 0 .1 91 / h、K1 2 0 .76 9/h、K2 1 0 .5 6 6 / h;灌服组血浆的药时数据符合一级吸收一室模型 ,动力学方程为 :C =6 .4 82 (e- 7.0 92 t- e- 1 0 .356 t) ,其主要药代动力学参数 :AU C1 5 .80 5 mg· L- 1 · h、Cmax2 .770 mg/ L、Tmax1 .5 0 0 h、t α4 .989h、Vd/ F2 .0 72 L/ kg、Ka7.0 92 /h、K 1 0 .35 6 / h。结果表明 ,腹腔注射给药比灌服给药吸收快 ,血药浓度达峰时间短于灌服给药 ,但血药浓度峰值明显高于灌服给药 (P<0 .0 5 ) ,血浆中恩诺沙星的回收率为 94 .5 79%。     

高效液相色谱法同时测定诺氟沙星和盐酸小檗碱的含量

以C18为固定相,0.1%磷酸溶液（用三乙胺调节pH值至3.5±0.1）-乙腈（70∶30）为流动相,348 nm为检测波长,采用高效液相色谱法同时测定诺氟沙星、盐酸小檗碱预混剂中诺氟沙星和盐酸小檗碱的含量。诺氟沙星和盐酸小檗碱线性范围分别为0.5-10μg和0.1-2μg,平均加标回收率分别为103.2%和97.7%,RSD分别为0.82%和1.3%（n=5）。     

诺氟沙星在鲤鱼体内的药代动力学

按 10 m g/ kg的剂量给鲤鱼肌注、口服诺氟沙星 ,用高效液相色谱法检测用药后不同时间血浆中药物的质量浓度 ,然后用 90 0 0 3P87实用药代动力学软件处理药时数据。结果 ,肌注和口服诺氟沙星在鲤鱼体内的药时数据均符合开放性二室模型。主要药代动力学参数 ,肌注 :t1/2α( 0 .12 79± 0 .0 130 ) h,t1/2β( 3.4 0 32±0 .5873) h,t1/2 ka( 0 .0 0 6 7± 0 .0 0 0 8) h,AU C ( 2 4 .94 81± 6 .314 6 )μg/ ( m L· h) ,CLS( 0 .4 0 0 8± 0 .10 35)mg/ ( kg· h) ,Tpeak( 0 .0 32 2± 0 .0 0 35) h,Cmax( 16 .8992± 4 .372 6 ) mg/ L;口服 :t1/2α( 3.4 0 71± 1.0 6 98) h,t1/2β( 77.12 39± 2 1.3875) h,t1/2 ka( 0 .14 91± 0 .0 130 ) h,K2 1( 0 .0 4 19± 0 .0 0 38) h- 1,K10 ( 0 .0 4 36±0 .0 0 2 1) h- 1,K12 ( 0 .12 70± 0 .0 30 1) h- 1,AU C ( 150 .6 0 2 9± 35.4 2 78)μg/ ( m L· h) ,CLS( 0 .0 6 6 4±0 .0 0 2 1) m g/ ( kg· h) ,Tpeak( 0 .730 0± 0 .0 10 2 ) h,Cmax( 5.7998± 1.36 75) m g/ L。肌注与内服的主要药代动力学参数差异显著 ( P <0 .0 1)。     

HPLC法测定盐酸小檗碱预混剂的含量

采用HPLC法测定盐酸小檗碱预混剂中盐酸小檗碱含量。色谱柱为Agilent ZORBAXSB-C18柱(3.9mm×150mm,4μm),流动相为0.02mol/L磷酸二氢钾溶液(用磷酸调pH为2.5)-乙腈(70∶30,V/V),检测波长346nm,流速1.0mL/min,柱温为30℃,保留时间约6.2min。盐酸小檗碱浓度在5~80μg/mL范围内,峰面积与浓度呈良好的线性关系(r2=0.9999)。平均回收率99.5%,RSD为0.4%。该方法适用于检测盐酸小檗碱预混剂。     

紫外分光光度法测定盐酸环丙沙星、盐酸小檗碱预混剂中盐酸小檗碱的含量

以0．05mol／L硫酸作对照液，用紫外分光光度法在421nm测定了盐酸环丙沙星、盐酸小檗碱预混剂中盐酸小檗碱的含量。结果表明，盐酸小檗碱在8-56μg／mL范围内，吸光度与浓度呈良好的线性关系，相关系数为0．9992，平均回收率为101．32％，RSD为0．94％（n=5）。本方法简便、快速、结果准确，适用于该制剂中盐酸小檗碱的质量分析检验。     

高效液相色谱法同时测定预混剂中盐酸环丙沙星和盐酸小檗碱含量

以C18为固定相,0.002 5 mol/L磷酸溶液(用三乙胺调pH值至3.0±0.1)-乙睛(75∶25)为流动相,335 nm为检测波长,采用高效液相色谱法同时测定盐酸环丙沙星、盐酸小檗碱预混剂中盐酸环丙沙星和盐酸小檗碱的含量。盐酸环丙沙星和盐酸小檗碱线性范围分别为1～600μg/mL和0.4～400μg/mL,平均加标回收率分别为100.0%和100.1%,RSD均为0.11%(n=5)。     

盐酸诺氟沙星在健康及细菌感染家蚕中的药代动力学研究

比较抗菌素盐酸诺氟沙星在健康和细菌感染家蚕间的药代动力学特征,可为临床合理用药提供科学依据。对健康及黑胸败血菌(Bacillus bombysepticus)感染家蚕幼虫用250μg/mL盐酸诺氟沙星药液处理的桑叶(剂量18mg/kg)添食,经高效液相色谱法(HPLC)检测不同时间的血浆药物浓度,并用MCP-KP药代动力学分析程序进行分析。结果表明,盐酸诺氟沙星在健康及细菌感染家蚕体内的血药浓度与时间关系均符合一级吸收一室开放模型。与健康家蚕药物代谢动力学参数相比较,盐酸诺氟沙星在细菌感染家蚕体内的药-时曲线下面积(AUC)由81.194mg/(h.L)降为66.105mg/(h.L),吸收半衰期(T1/2Ka)由1.252h延长为1.591h,分布半衰期(T1/2α)由2.673h缩短为1.981h,消除半衰期(T1/2β)由9.298h缩短为5.338h,说明细菌感染使盐酸诺氟沙星在家蚕体内的吸收能力下降,吸收减慢,分布和消除加快。     

盐酸小檗碱在鸡体内的药动学研究

探讨盐酸小檗碱在鸡体内的药动学特征。鸡以3mg／kg和50mg／kg剂量静脉注射和口服给药,采用HPLC法测定血浆中盐酸小檗碱的质量浓度。血药浓度-时间数据经DAS药代动力学分析软件处理,计算出药动学参数。结果表明：盐酸小檗碱静脉注射药时曲线符合三室开放模型,主要药动学参数分别为：t1／2β为（0．41±0．24）h,t1／2γ为（3．66±1．06）h,Vc为（25．49±21．77）L·kg^-1,CL为（43．20±16．21）L·h^-1·kg^-1,AUC为（78．92±30．58）μg·L^-1·h。盐酸小檗碱口服给药的药时曲线符合二室开放模型,主要药动学参数分别为：t1／2α为（1．87±0．76）h,t1／2β为（4．18±3.14）h,t1／2ka为（0．89±0．46）h,Tmax为（2．64±0．63）h,Cmax为（4．09±0．11）μg·L^-1,AUC为（26．18±10．73）μg·L^-1·h,绝对生物利用度为2．03％。鸡口服盐酸小檗碱的生物利用度低,消除较快。     

酒石酸泰万菌素预混剂在仔猪体内的药代动力学研究

为研究酒石酸泰万菌素预混剂在仔猪体内的药物动力学特征,采用平行试验设计方法,将12头28日龄健康仔猪随机分为两组,每组6头（公猪）,第1组口服沈阳伟嘉生物技术有限公司的酒石酸泰万菌素预混剂,第2组口服英国伊科拜克动物保健品有限公司的酒石酸泰万菌素预混剂。两组给药剂量相同均为125mg/kg,所有仔猪给药前禁食12h,给药6h后恢复正常饮食。给药后按照预定的采血点采集血样,用液相色谱-质谱法（LC/MS-MS）测定酒石酸泰万菌素预混剂的血浆浓度,用DAS 2.1.1 软件计算药动学参数。结果显示：口服沈阳伟嘉生物技术有限公司的酒石酸泰万菌素预混剂在仔猪体内主要药动学参数如下：平均最高血药浓度（Cmax）为247.3 ng/ml,平均药时曲线下面积（AUC）为1899.0 ng/ml*h,平均达峰时间（Tmax）为1 h;口服英国伊科拜克动物保健品有限公司的酒石酸泰万菌素预混剂主要药动学参数如下：平均最高血药浓度（Cmax）为159.8 ng/ml,平均药时曲线下面积（AUC）为986.0 ng/ml*h,平均达峰时间（Tmax）为1.5 h;结果表明,沈阳伟嘉生物技术有限公司的酒石酸泰万菌素预混剂平均最高血药浓度（Cmax）是参比制剂的1.55倍,平均药时曲线下面积（AUC）是参比制剂的1.93倍,生物利用度是参比制剂的193%;沈阳伟嘉生物技术有限公司的酒石酸泰万菌素预混剂相比参比制剂（英国伊科拜克动物保健品有限公司）具有给药后仔猪体内分布迅速,血药浓度高,药时曲线下面积（AUC）高,生物利用度高,吸收和代谢速度快,药物残留时间短,休药期短,对减少抗生素残留具有重要意义。     

盐酸多西环素在猪体内的药物动力学及其残留

试验建立了反相高效液相色谱(RT-HPLC)法测定盐酸多西环素的浓度,探讨了盐酸多西环素在猪体内的药物动力学和残留特征。结果表明,盐酸多西环素以2.5mg/kg单剂量肌内注射给猪(n=6),药物动力学模型符合有吸收一室模型,药物动力学参数:吸收半衰期(t1/2ka)、消除半衰期(t1/2ke)为(0.400±0.312)h、(9.530±0.956)h,药时曲线下面积(AUC)为(44.414±4.123)mg·h·L-1,最大血药浓度(Cmax)为(2.811±0.136)mg/L,达峰时间(Tp)为(1.910±0.213)h。另外,以相同剂量肌内注射给猪(n=6),每天1次,连续给药4d后,在不同时间测定盐酸多西环素在猪的肌肉、肝脏、肾脏、皮肤和脂肪中的残留量。在给药后16d,盐酸多西环素在各组织均能检测到,且残留均低于残留限量。盐酸多西环素注射液在猪体内消除缓慢,残留期较长,建议休药期不低于16d。     

Pharmacokinetics of tapentadol in laying hens and its residues in eggs after multiple oral dose administration

1. The aim of the study was to evaluate the pharmacokinetics (PKs) of tapentadol (TAP), a novel opioid analgesic, in laying hens after intravenous (IV) and oral (PO) administration and to quantify the concentrations of TAP residues in eggs.

2. Twenty healthy laying hens were divided into three groups: A (n = 6), B (n = 6) and C (n = 8). The study was conducted in two phases. Groups A and B received TAP by IV and PO routes at the dose of 1 and 5 mg/kg, respectively.

3. No visible adverse effects were observed after administration of the drug. TAP plasma concentrations were detectable up to 4 h following administration. Following IV administration, TAP plasma concentrations were only higher than the minimal effective concentration (148 ng/ml) reported for humans for 1 h. After single PO administration, plasma concentrations of TAP would not conform to software algorithms and the PK parameters were not calculated. TAP concentration following multiple PO doses at 5 mg/kg for 5 d was found to be higher and more persistent (12 h vs. 7 h) in yolk compared with albumen.

4. This is the first PK study on the novel atypical opioid TAP in laying hens. Further studies are required to investigate the analgesic efficacy and actual effective plasma concentration of TAP in this species.     

Pharmacokinetics,efficacy and convulsive dose of articaine hydrochloride in goat kids

ObjectiveTo investigate the pharmacokinetics, efficacy and convulsive dose of articaine hydrochloride in goat kids.Study designExperimental prospective study.AnimalsA total of 18 (n = 6 animals per experiment) male Saanen goat kids (2–4 weeks old).MethodsThe study consisted of three experiments. The first determined the pharmacokinetics of articaine following intravenous administration of articaine hydrochloride (8 mg kg^–1). The second experiment investigated the anaesthetic efficacy and pharmacokinetics following cornual nerve block using 1.5% articaine hydrochloride. Anaesthesia of horn buds was evaluated using the response to pinprick test. Non-compartmental analysis was used. The final experiment determined the convulsive dose of articaine and its corresponding plasma concentration following intravenous infusion of articaine hydrochloride (4 mg kg^–1 minute^–1). Data are shown as mean ± standard deviation.ResultsThe mean terminal half-life (t_1/2λz), mean volume of distribution at steady state (Vd_ss) and mean plasma clearance (CL) of articaine following intravenous administration were 0.66 hour, 3.81 L kg^–1 and 5.33 L hour^–1 kg^–1, respectively. After cornual nerve block, the mean maximum plasma concentration of articaine was 587 ng mL^–1 at 0.22 hour and its mean t_1/2λz was 1.26 hours. Anaesthesia of horn buds was observed within 4 minutes following cornual nerve block. The mean dose required to produce convulsions was 16.24 mg kg^–1 and mean convulsive plasma concentrations of articaine and articainic acid were 9905 and 1517 ng mL^–1, respectively.ConclusionsIntravenous administration of 8 mg kg^–1 of articaine hydrochloride did not cause any adverse effects. Pharmacokinetic data suggest that articaine was rapidly eliminated and cleared. Cornual nerve block using 1.5% articaine hydrochloride alleviated the response to the acute nociceptive stimulus during disbudding.Clinical relevanceArticaine hydrochloride appears to be a safe and effective local anaesthetic for disbudding in goat kids.     

Pharmacokinetics and tissue residues of enrofloxacin in the largemouth bass (Micropterus salmoides) after oral administration

The study was carried out to evaluate the pharmacokinetic disposition of enrofloxacin (ENF) with a single dose of 20 mg/kg after oral administration in largemouth bass (Micropterus salmoides) at 28°C. The concentrations of ENF and of its metabolite ciprofloxacin (CIP) in plasma, liver, and muscle plus skin in natural proportions were determined using HPLC. The concentration–time data for ENF in plasma were best described by a two-compartment open model. After oral administration, the maximum ENF concentration (C_max) of 10.99 μg/ml was obtained at 0.60 hr. The absorption half-life (T_1/2Ka) of ENF was calculated to be 0.07 hr whereas the elimination half-life (T_1/2β) of the drug was 90.79 hr. The estimates of area under the plasma concentration–time curve (AUC) and apparent volume of distribution (Vd/F) were 1,185.73 μg hr/ml and 2.21 L/kg, respectively. ENF residues were slowly depleted from the liver and muscle plus skin of largemouth bass with the T_1/2β of 124.73 and 115.14 hr, respectively. Very low levels of ciprofloxacin were detected in the plasma and tissues. A withdrawal time of 24 days was necessary to ensure that the residues of ENF + CIP in muscle plus skin were less than the maximal residue limit (MRL) of 100 μg/kg established by the European Union.     

Pharmacokinetics of articaine hydrochloride and its metabolite articainic acid after subcutaneous administration in red deer (Cervus elaphus)

AIM: To develop and validate a simple and sensitive method using liquid chromatography-mass spectrometry (LC-MS) for quantification of articaine, and its major metabolite articainic acid, in plasma of red deer (Cervus elaphus), and to investigate the pharmacokinetics of articaine hydrochloride and articainic acid in red deer following S/C administration of articaine hydrochloride as a complete ring block around the antler pedicle.

METHODS: The LC-MS method was validated by determining linearity, sensitivity, recovery, carry-over and repeatability. Articaine hydrochloride (40?mg/mL) was administered S/C to six healthy male red deer, at a dose of 1?mL/cm of pedicle circumference, as a complete ring block around the base of each antler. Blood samples were collected at various times over the following 12 hours. Concentrations in plasma of articaine and articainic acid were quantified using the validated LC-MS method. Pharmacokinetic parameters of articaine and articainic acid were estimated using non-compartmental analysis.

RESULTS: Calibration curves were linear for both articaine and articainic acid. The limits of quantifications for articaine and articainic acid were 5 and 10?ng/mL, respectively. Extraction recoveries were >72% for articaine and >68% for articainic acid. After S/C administration as a ring block around the base of each antler, mean maximum concentrations in plasma (C_max) of articaine were 1,013.9 (SD 510.1) ng/mL, detected at 0.17 (SD 0.00) hours, and the C_max for articainic acid was 762.6 (SD 95.4) ng/mL at 0.50 (SD 0.00) hours. The elimination half-lives of articaine hydrochloride and articainic acid were 1.12 (SD 0.17) and 0.90 (SD 0.07) hours, respectively.

CONCLUSIONS AND CLINICAL RELEVANCE: The LC-MS method used for the quantification of articaine and its metabolite articainic acid in the plasma of red deer was simple, accurate and sensitive. Articaine hydrochloride was rapidly absorbed, hydrolysed to its inactive metabolite articainic acid, and eliminated following S/C administration as a ring block in red deer. These favourable pharmacokinetic properties suggest that articaine hydrochloride should be tested for efficacy as a local anaesthetic in red deer for removal of velvet antlers. Further studies to evaluate the safety and residues of articaine hydrochloride and articainic acid are required before articaine can be recommended for use as a local anaesthetic for this purpose.     

苯巴比妥的毒副作用及其残留检测

本文就苯巴比妥(PB)的化学结构、理化特性、构效关系、毒副作用、在动物体内的代谢残留以及检测方法等进行详尽阐述。