Pharmacokinetics of detomidine administered to horses at rest and after maximal exercise

Reason for performing study: Increased doses of detomidine are required to produce sedation in horses after maximal exercise compared to calm or resting horses. Objectives: To determine if the pharmacokinetics of detomidine in Thoroughbred horses are different when the drug is given during recuperation from a brief period of maximal exercise compared to administration at rest. Methods: Six Thoroughbred horses were preconditioned by exercising them on a treadmill. Each horse ran a simulated race at a treadmill speed that caused it to exercise at 120% of its maximal oxygen consumption. One minute after the end of exercise, horses were treated with detomidine. Each horse was treated with the same dose of detomidine on a second occasion a minimum of 14 days later while standing in a stocks. Samples of heparinised blood were obtained at various time points on both occasions. Plasma detomidine concentrations were determined by liquid chromatographymass spectrometry. The plasma concentration vs. time data were analysed by nonlinear regression analysis. Results: Median back‐extrapolated time zero plasma concentration was significantly lower and median plasma half‐life and median mean residence time were significantly longer when detomidine was administered after exercise compared to administration at rest. Median volume of distribution was significantly higher after exercise but median plasma clearance was not different between the 2 administrations. Conclusions and potential relevance: Detomidine i.v. is more widely distributed when administered to horses immediately after exercise compared to administration at rest resulting in lower peak plasma concentrations and a slower rate of elimination. The dose requirement to produce an equivalent effect may be higher in horses after exercise than in resting horses and less frequent subsequent doses may be required to produce a sustained effect.     

亚甲基蓝在鲤体内消除规律研究

为探究常规用药条件下亚甲基蓝及其代谢物在水产动物体内的分布和消除规律,以鲤(Cyprinuscarpio)为研究对象,以质量浓度为15 mg/L的亚甲基蓝溶液浸泡试验鱼0.5 h后,将其饲养于水族箱中,采用高效液相色谱-质谱串联法检测亚甲基蓝及其代谢物在鲤各组织中的质量浓度,采用PK Solver药动学药效学数据处理软...     

川续断皂苷乙对氟苯尼考在大鼠体内的药动学影响

研究川续断皂苷乙对氟苯尼考在大鼠体内药动学影响.将24只大鼠(200±10)g随机分成两组,每组12只.试验组连续7 d灌胃川续断皂苷乙(60 mg/kg,1次/d),对照组给予相同体积的生理盐水,第8天两组各6只大鼠灌服氟苯尼考(30 mg/kg)后按时间点连续采血,采用高效液相色谱法检测氟苯尼考血药浓度,数据采用D...     

2-Methylisoborneol disposition in three strains of catfish: absence of biotransformation

2-Methylisoborneol (MIB) and structurally related terpenoid compounds are responsible for millions of dollars of lost revenue to catfish farmers. In an attempt to determine enzymatic pathways of biotransformation and elimination of MIB, the in vitro metabolism of MIB was examined in the Ulvade strain of channel catfish (Ictalurus punctatus). Although cytochrome P450 (CYP) activities were observed and correlated with expression of specific isoforms (i.e. steroid hydroxylation and CYP3A expression), no metabolites of MIB were observed. To determine whether extrahepatic biotransformation may be occurring the in vivo metabolism and disposition of ¹⁴C-MIB was examined in Uvalde, USDA-103 channel catfish, and a channel catfish X blue catfish (Ictalurus furcatus) hybrid species. Confirming in vitro hepatic studies, no metabolites were observed in plasma from animals treated with an intra-arterial dose of ¹⁴C-MIB. ¹⁴C-MIB elimination was predicted using a two compartment model in each strain of fish. There was no significant difference in terminal half-lives between strains but possible differences in total body clearance and apparent volumes of distribution which may be related to higher lipid content in the hybrids. Results of these studies indicate biotransformation has no involvement in MIB elimination and that other physiological processes may play a more significant role in MIB disposition within Ictalurid fish species.     

猪饥饿和喂饲后内服氟甲砜霉素的药动学比较

报道了猪饥饿及喂饲后 5min单剂量 (2 0mg/kg)内服氟甲砜霉素的药动学比较的研究 .用高效液相色谱法测定血药浓度 .试验所得的血浆浓度 时间数据采用非房室模型统计矩原理分析处理 .猪饥饿后内服给药的主要药物动力学参数 :AUC =(91 40± 7 5 1)mg·h/L ,MRT =(7 15± 0 5 8)h ,t1/ 2 β=(5 99± 0 2 6 )h .猪喂饲后 5min内服给药的主要药物动力学参数为 :AUC =(88 47± 2 2 1)mg·h/L ,MRT =(10 94± 1 0 6 )h ,t1/ 2 β=(6 44± 0 90 )h .试验结果表明 ,猪喂饲后内服氟甲砜霉素的生物利用度与饥饿后的相似 ,但峰浓度显著小于饥饿后的峰浓度 ,两者的消除半衰期相似 .     

吡喹酮脂质体在山羊体内的代谢动力学研究

为了探明吡喹酮脂质体在山羊体内的代谢动力学,给山羊1次静脉推注吡喹酮脂质体3mg/kg,取24h内不同间隔时间的血样测血药质量浓度.结果表明,血药质量浓度-时间曲线符合无吸收因素的一室开放模型,其药物代谢动力学参数:消除半衰期为(10.00±0.59)h;消除速率常数β为(0.069±0.004)h-1;初始质量浓度为(18.81±0.46)μg/100mL;维持有效质量浓度时间为(20.01±1.18)h;表观分布容积为(2.91±0.42)100mL/kg;清除率为(1.93±0.29)100mL/(kg·h);药时曲线下面积为(271.67±21.07)μg·h/100mL.     

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.     

恩诺沙星在健康兔和人工感染巴氏杆菌兔体内的药代动力学研究

应用反相高效液相色谱法,对肌肉注射了恩诺沙星（Ｅｎｒｏｆｌｏｘａｃｉｎ） 的６ 只健康兔和６ 只人工感染巴氏杆菌兔体内的血药浓度进行了测试和药代动力学研究。应用非线性最小二乘法处理,实验数据参数用一室模型很好地描述。肌肉注射给药后,经过短暂的迟滞期（Ｌａｇｔｉｍｅ（ 健兔） ＝ ３－４６６４ ±１－１４９０ ｍｉｎ ,Ｌａｇｔｉｍｅ（ 病兔） ＝４－１９８４ ±０－９６１５ ｍｉｎ） ,血药浓度迅速上升,分布相很快完成（ｔ１／２ｋａ（ 健兔） ＝ ６－６４３２ ±３－６６７７ ｍｉｎ ,ｔ１／２ｋａ（病兔） ＝ ５－４８８４ ±１－９３３７ ｍｉｎ, 达峰时间ｔｐ（ 健兔） ＝ ３９－１９７２ ±１１－８９５１ ｍｉｎ ,ｔｐ（ 病兔） ＝ ２７－４６７０ ±６－０１２１ ｍｉｎ） 。之后,是一缓慢的消除相（ｔ１／２ｋｅｌ（ 健兔） ＝ ２４２－７０８０ ±５２－２７６５ ｍｉｎ,ｔ１／２ ｋｅｌ（ 病兔） ＝ １６０－８２３８ ±６６－１２７３ ｍｉｎ） ,表观分布容积Ｖｄ（ 健兔） ＝ ２－６４７０ ±１－５４１８ Ｌ／ｋｇ,Ｖｄ（ 病兔） ＝ １－５２２９ ±０－４２８０ Ｌ／ｋｇ 。机体清除率为ＣＬＢ（ 健兔） ＝ ７－１０００ ±２－６０００ ｍＬ／（ｋｇ·ｍｉ     

罗美沙星在鸡体内的药物动力学与生物利用度研究

采用反向高效液相色谱法, 研究了罗美沙星在健康鸡体内的药动学与生物利用度。结果表明, 鸡静注罗美沙星后的ｃｉ－ ｔｉ数据符合二室开放模型, 其主要动力学参数如下： ｔｔ／２α０５６±０１２ｈ, ｔ１／β７６９±０７９ ｈ, Ｖｄ２１６±０３５ Ｌ／ｋｇ, Ｃ Ｌ Ｂ０２０±００３ Ｌ／ｋｇ·ｈ, Ａ Ｕ Ｃ ５２１９±８９９ ｕｇ／ｍ Ｌ·ｈ。鸡内服、肌注罗美沙星ｃ１－ ｔ１ 数据, 均符合有吸收因素二室模型, 内服的主要动力学参数如下： ｔ１／２ｋａ１１８±０１４ ｈ、ｔ１／２α２４５±０４６ ｈ、ｔ１／２β１７２１±１５８ ｈ、 Ａ Ｕ Ｃ ３８７８±６３３ ｕｇ／ｍ Ｌ·ｈ、ｔｍａｘ３１６＋ ０２３ ｈ、 Ｃｍ ａｘ２０６±０４３ ｕｇ／ｍ Ｌ、 Ｆ７４３１％ ; 肌注的主要动力学参数是： ｔ１／２ｋａ０６７±０１２ ｈ、ｔ１／２α１３０±０２３ ｈ、ｔ１／２β１１５２±１０２ｈ、 Ａ Ｕ Ｃ ４３１５±２０４ ｕｇ／ｍ Ｌ·ｈ、ｔｍ ａｘ１７６±０２０ ｈ、 Ｃｍａｘ４６０±ｕｇ／ｍ Ｌ、 Ｆ８２６８％ 。本文还就罗美沙星的临床应用进行了药动学评价。