Pharmacokinetics of Quinocetone and Its Major Metabolites in Swine After Intravenous and Oral Administration

The pharmacokinetics of quinocetone and its major metabolites in healthy swine was investigated in this paper.Quinocetone was administered to 8 healthy cross-bread swine intravenously and orally at a dosage of 4 and 40 mg kg-1 body weight respectively in a randomized crossover design test with two-week washout period.A sensitive highperformance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method was developed for the determination of quinocetone and its metabolite 1-desoxyquinocetone in plasma.Plasma concentration versus time profiles of quinocetone and its metabolite l-desoxyquinocetone were analyzed by non-compartmental analysis using Winnonlin 5.2 software.Mean maximum concentrations (Cmax) for quinocetone was found to be (0.56±0.13) μg mL-1 at 2.92 h,after oral administration of quinocetone.Mean maximum concentrations (Cmax) for l-desoxyquinocetone after intravenous or oral administration of quinocetone were (0.0095±0.0012) μg mL-1 at 0.083 h and (0.0067±0.0053) μg mL-1 at 3.08 h.The apparent elimination half-lives (T1/2) for quinocetone and its metabolite 1-desoxyquinocetone were (2.24±0.24) and (5.23±0.56) h after intravenous administration of quinocetone and (2.91±0.29) and (11.85±2.89) h after oral administration of quinocetone,respectively.Mean areas under the plasma concentration-time curve (AUC0-∞) for quinocetone and 1-desoxyquinocetone were (2.02±0.15) and (0.2±0.002) μg h mL-1 respectively after intravenous administration of quinocetone,and (3.5±0.79) and (0.053±0.03) μg h mL-1 after oral administration of quinocetone,respectively.Quinocetone was rapidly absorbed and metabolized in swine after oral and intravenous administration.The plasma concentration-time curve (AUC0-∞) of 1-desoxyquinocetone were much smaller than those of quinocetone,while the elimination half-lives (T1/2) were much longer than those of quinocetone after intravenously (i.v.) or oral administration.     

恩诺沙星在杂交鲟体内的药物代谢动力学

采用高效液相色谱法,研究在单次口灌给药途径下,恩诺沙星在杂交鲟（施氏鲟Acipenser schrenckii♂×达氏鳇Huso dauricus♀）体内的药代动力学。对杂交鲟单次口灌给药恩诺沙星10 mg/kg后,用3P97药代动力学分析软件对实验数据进行了分析。结果表明：恩诺沙星在杂交鲟血液、肌肉和肝脏中的药物时量曲线关系符合一级吸收的二室开放模型;该药在血液、肌肉和组织中的平均回收率分别为93.6%±1.14%、92.65%±1.5%、92.82%±1.39%,在杂交鲟不同组织中分布较广,其在血液、肌肉和肝脏的表观分布容积v/f分别为26.987、6.2298、2.1515 L/kg;恩诺沙星在杂交鲟体内消除较慢,在血液、肌肉和肝脏中的消除半衰期分别为290.139、114.9、901.835 h,总体清除率分别为0.2288、0.1047、0.02164 L/（kg.h）。鉴于恩诺沙星在杂交鲟体内消除较慢,建议养成阶段使用其它药物。     

氟氯苯菊酯在犬体内的药动学初步研究

研究自制1%氟氯苯菊酯浇泼剂在健康家犬体内的药代动力学特征。选用6条健康犬,以2mg/kg单剂量沿背中线浇泼,采用反相高效液相色谱法(RP-HPLC)测定犬血浆中氟氯苯菊酯浓度,用3P97药动软件处理药时数据,计算药代动力学参数。氟氯苯菊酯的药时数据符合一级吸收二室开放模型,主要药动学参数为:T1/2α为(3.622±1.079)h,T1/2β为(22.654±0.417)h,T1/2Ka为(1.684±0.240)h,AUC为(47.385±1.709)μg.mL-1.h,Tpeak为(4.165±0.187)h,Cmax为(1.902±0.064)μg/mL,Lagtime为(0.489±0.002)h。健康家犬单次给予氟氯苯菊酯浇泼剂后,吸收、消除均缓慢,药物在动物体内作用时间较长。     

唑拉西泮和替来他明对中华草龟的麻醉效果及其药物代谢动力学

为了解龟类临床兽医学的麻醉术问题,根据预实验结果选择动物医学推荐的临床麻醉药物舒泰(唑拉西泮:替来他明=1∶1)对中华草龟进行麻醉实验,比较不同注射剂量的舒泰对中华草龟的麻醉效果,并使用高效液相色谱法(HPLC)测定舒泰中唑拉西泮和替来他明在中华草龟血浆中的浓度,用药物代谢动力学软件PKsolver 2.0来分析其药物代谢动力学特征。结果发现,肌肉注射舒泰剂量为25 mg/kg时,对中华草龟麻醉的诱导期、麻醉期和苏醒期的时长分别为0.42、4.33和4.14 h,舒泰对中华草龟的麻醉效果较好,符合临床手术的要求。唑拉西泮和替来他明在中华草龟体内的药时曲线均符合一次式二室开放模型,唑拉西泮的药物代谢动力学方程为C=13.462e~(–0.223t)+2.127e~(–0.055t),主要药物代谢动力学参数为达峰浓度C_(max)=11.695μg/mL、达峰时间T_(max)=1.060 h和药时曲线下面积AUC=92.470μg/(mL·h);替来他明的药物代谢动力学方程为C=10.619e–0.203t+0.279e–0.047t,主要药物代谢动力学参数为达峰浓度Cmax=9.654μg/mL、达峰时间Tmax=0.482 h和药时曲线下面积AUC=56.348μg/(mL·h)。结合麻醉效果分析,唑拉西泮和替来他明血药浓度分别达到8.12和8.96μg/mL时,可以使健康的中华草龟进入麻醉期,为维持麻醉状态,唑拉西泮和替来他明的血药浓度应不低于7.18和4.73μg/mL。     

Pharmacokinetic/pharmacodynamic properties and P‐glycoprotein expression in pacific white shrimp,Litopenaeus vannamei after oral administration at three dosages of oxolinic acid

The experiments explored the pharmacokinetics (PK) properties of oxolinic acid (OXA) after oral administration at three dosages (10, 30 and 80 mg/kg) via medicated feed in the shrimp. The results showed that the C_max values of 4.31, 14.93 and 16.62 mg/L and AUC_0–∞ values of 92.61, 252.30 and 364.27 mg hr^?1 L^?1 were observed at three OXA dosage groups in the haemolymph respectively. In the hepatopancreas, C_max values of 7.90, 27.23 and 60.51 mg/kg and AUC_0–∞ values of 42.01, 133.06 and 219.06 mg hr^?1 L^?1 were observed at 0.5 hr post administration respectively. In the muscle, C_max values of 1.62, 5.80 and 7.36 mg/kg and the AUC_0–∞ values of 25.64, 98.10 and 134.24 mg hr^?1 L^?1 were observed at 2 hr post administration respectively. In the gills, C_max values of 2.87, 8.08 and 12.12 mg/kg and the AUC_0–∞ values of 51.38, 118.65 and 206.48 mg hr^?1 L^?1 were observed at 4 hr post administration respectively. In addition, the in vitro MIC values of OXA at three dosages against 132 strains of Vibrio were examined and showed that the minimum inhibitory concentration (MIC) values for OXA primarily ranged from 0.15–1.25 µg/ml, including eight strains of Vibrio showing MIC values ≥5 µg/ml. The MIC₅₀ and MIC₉₀ values of 132 strains were 0.62 and 1.25 μg/ml respectively. The AUC_0–24/MIC₉₀ ratios of Vibrio were 140.4 in 30 mg/kg group. Furthermore, the P‐glycoprotein (P‐gp) expression was determined in shrimp tissues after administration to three dosage groups (10, 30 and 80 mg/kg). The results showed that P‐gp expression was up‐regulated in the hepatopancreas (5.36‐, 13.68‐ and 31.06‐fold respectively) compared with the control group.     

液相色谱—串联质谱法研究恩诺沙星在中华草龟体内的药物代谢动力学

为研究不同给药方式下，恩诺沙星在中华草龟体内的药物代谢动力学规律，实验选取20只健康中华草龟，每组10只，随机分为2组，分别为肌注组和胃插管强制口服组，给药量均为10 mg/kg，应用液相色谱—串联质谱法测定数据，Kinetic 4.4软件的非房室模型分析药时数据。胃插管强制口服给药主要药动学参数为C_max7.49 μg/mL、T_max 12 h、T_1/2λz为99.85 h、AUC_0-∞为531.67 μg/(mL·h)；肌注给药主要药动学参数为C_max 5.85 μg/mL、T_max 4 h、T_1/2λz为30.42 h、AUC_0-∞为193.6 μg/(mL·h)。2种不同给药条件下，肌注恩诺沙星比胃插管强制口服更快达到最高血药浓度，表明肌注恩诺沙星在中华草龟体内吸收更快；胃插管强制口服给药的C_max和AUC均高于肌注给药，表明胃插管强制口服恩诺沙星在中华草龟体内吸收更完全，分布更广泛，效果更好。恩诺沙星在中华草龟体内消除缓慢，滞留时间(MRT)长，胃插管强制口服给药MRT显著长于肌注给药，其血药浓度保留时间长，效果更持久。研究表明，需较快达到疗效时，建议肌注恩诺沙星；需持续给药且龟体代谢状态正常时，建议胃插管强制口服恩诺沙星；恩诺沙星在胃插管强制口服给药条件下，在中华草龟体内血药浓度高、保留时间长、生物利用度高，更适宜作为中华草龟个体疾病治疗的给药方式。     

阿苯达唑纳米混悬剂的研制及其评价

为了解决阿苯达唑的溶解性和口服吸收难题，借助高分子活性剂的稳定作用，利用反溶剂法-高压匀质法制备阿苯达唑纳米混悬剂，并考察该制剂的药学特征及稳定性；研究该制剂在大鼠体内的药代动力学。研究创制的纳米混悬液在电镜下药物形状大小均一，中位粒径为358.1nm。其药学特征符合《兽药质量标准》（2017版）中对混悬液的质量要求。6个月加速试验表明，该制剂外观色泽、含量、pH值、沉降体积比、重分散性均未发生明显变化，且放置6个月后粒径没有显著变化。该阿苯达唑纳米混悬液的Cmax为5.895μg/mL，显著高于参比制剂阿苯达唑伊维菌素粉、佛山正典阿苯达唑混悬液的2.804和2.053μg/mL。与阿苯达唑伊维菌素粉、佛山正典阿苯达唑混悬液相比，该制剂的相对生物利用度分别为214% 和299.74% ，表明该阿苯达唑纳米混悬液能显著提高阿苯达唑的吸收，将有助于提高临床治疗效果。     

长效土霉素注射液的研究进展

综述了土霉素注射液在处方、局部刺激和局部残留、药代动力学、生物药剂学和在动物体内残留等方面的研究进展。     

马波沙星研究进展

马波沙星作为一种专用于动物的新型第3代氟喹诺酮类广谱抗菌药，其可作用于狗、猫、猪、牛等动物的呼吸道、消化道、泌尿道及皮肤感染问题，具有吸收快速且彻底、对组织渗透性强、分布范围广泛特点，同时，其在血浆和组织中的含量较高，可消除半衰期长、生物利用率高的良好特性。本文主要对马波沙星的作用机制、药动学、药效学及临床使用、不良影响及注意事项进行综述，为马波沙星在临床使用中提供一定的参考价值。     

恩诺沙星及其代谢物环丙沙星在欧洲鳗鲡体内的代谢动力学

采用高效液相色谱法,研究药饵口灌给药途径下,恩诺沙星及其代谢物环丙沙星在欧洲鳗鲡(Anguilla anguilla)体内的药代动力学。欧洲鳗鲡口灌给药恩诺沙星10 mg/kg后,其血浆、肌肉和肝脏中药物时量曲线关系符合一级吸收的二室开放动力学模型。恩诺沙星在欧洲鳗鲡不同组织中分布较广,血浆、肌肉和肝脏的Vd分别为6.362 L/kg、8.081 L/kg和15.870 L/kg;恩诺沙星在鳗鲡体内消除较慢,在血浆、肌肉和肝脏中的消除半衰期(tβ1/2)分别为161.10 h、333.21 h和611.26 h,总体清除率(CLs)分别为27.4 mL/(kg.h)、16.8 g/(kg.h)和18.0 g/(kg.h)。代谢物环丙沙星在鳗鲡血浆、肌肉和肝脏中药物水平的变化趋势与恩诺沙星基本相似,呈现出多峰现象,但3种组织中环丙沙星出现第一个药峰时间分别为给药后第24小时、24小时和12小时,3种组织中环丙沙星峰值水平肝脏中最高、肌肉中次之、血浆中最低,环丙沙星在肌肉和肝脏中的消除速率比较缓慢。鉴于恩诺沙星和其代谢物环丙沙星在欧洲鳗鲡体内消除较慢,建议养成阶段使用其他药物。