肌注和口灌氟苯尼考在吉富罗非鱼体内的药代动力学

通过肌内注射、口灌两种给药方式,研究氟苯尼考在罗非鱼体内的药物代谢动力学特征。把吉富罗非鱼(GIFT Oreochromis niloticus)随机分成2组,控制水温在30℃,以15 mg/kg分别单剂量肌内注射、口灌给药。经高效液相色谱法(HPLC)测定血浆中氟苯尼考浓度,用Win Nonlin药动学软件分析药动学参数。结果表明:肌内注射氟苯尼考后,药物吸收较慢,消除较快,达峰时间(T_(max))=4 h,峰浓度(C_(max))=4.64μg/mL,消除半衰期(T_(1/2λ)z L)=10.45 h,药-时曲线下面积(AUC)=91.06μg·h/mL。口灌氟苯尼考后,药物吸收较快,消除较慢,T_(max)=1 h,C_(max)=5.92μg/mL,T_(1/2λ)z L=13.13 h,AUC=61.96μg·h/mL。肌内注射、口灌氟苯尼考后,二者的药动学参数差异显著,这一差异表明肌内注射给药吸收相对较慢,但更为完全(肌内注射氟苯尼考的AUC明显较大),消除相对较快。     

Pharmacokinetics and the active metabolite of enrofloxacin in Chinese mitten-handed crab (Eriocheir sinensis)

The pharmacokinetics and active metabolite of enrofloxacin were estimated after single intramuscular administration (10.0 or 20.0 mg/kg body weight) to the Chinese mitten-handed crab (Eriocheir sinensis) in fresh water at 25.0 ± 1.0 °C. Levels of enrofloxacin and its metabolite ciprofloxacin in the main tissues (hemolymph, hepatopancreas, muscle, ovary and spermary) were simultaneously detected by HPLC. Enrofloxacin concentration–time profiles for the hemolymph in both tests were described by a two-compartment open model with first-order absorption. Distribution half-time (T_1/2), elimination half-time (T_1/2β), body clearance (CL/F), mean residence time (MRT_0–∞), area under the concentration–time curve from 0 to ∞ h (AUC_0–∞) and apparent volume of distribution (Vd/F), which derived from the pharmacokinetic model, were 0.427 h, 21.3 h, 0.133 l/h/kg, 60.0 h, 96.9 μg/ml/h and 4.08 l/kg, respectively, at a dose of 10.0 mg/kg body weight, and 0.216 h, 12.3 h, 0.189 l/h/kg, 85.8 h, 187 μg/ml/h and 3.35 l/kg, respectively, at a dose of 20.0 mg/kg body weight. Similarities were found between the hemolymph concentration–time curves of the two tests; for example, instant absorption process followed by the distribution phrase, and a second absorption peak at 6 h post-treatment. After intramuscular administration of 10.0 mg/kg body weight, absorption of enrofloxacin was observed in the main edible tissues (hepatopancreas, muscle, ovary and spermary), and the drug residue was the highest in the hepatopancreas, where the ‘drug sink’ phenomenon occurred. Comparative pharmacokinetics showed fast absorption, broad distribution and fast elimination of enrofloxacin in E. sinensis after intramuscular dosing. Regarding ciprofloxacin, the main active metabolite of enrofloxacin, though relatively low levels were detected in all the main tissues of the crab, its kinetics in the hemolymph in the two tests were not described by a one- or two-compartment open model.     

Hepatopancreatic and muscular distribution of oxytetracycline antibiotics in farmed pacific white shrimp (Penaeus vannamei): a physiological‐based pharmacokinetic model approach

Oxytetracycline (OTC) pharmacokinetic models previously used to investigate Penaeus vannamei have not addressed the specific problems related to drug distribution/disposition in particular tissues. This study aimed to provide an insight into OTC kinetics in the hepatopancreas and muscle based on a physiological model approach. Adult male P. vannamei at the C‐D₀ inter‐moulting stage were randomly assigned to intra‐sinus and oral administrations. In the intra‐sinus group, shrimps were dosed via the ventral sinus at an OTC level of 10.0 μg g^?1 body weight, while in the oral one, they were force fed at a dose level of 50.2 μg g^?1. The medicated animals were sampled at various time intervals until 170 h after dosing. Haemolymph, muscle and hepatopancreas samples were taken and OTC levels were determined using the validated HPLC method. A model focused on the hepatopancreas and muscle was developed. Oxytetracycline pharmacokinetic profiles in particular tissues were fitted into the model with an R² of between 0.6568 and 0.9904. Oxytetracycline muscular distributions were essentially identical for both groups and the drug did not accumulate in muscle. The distributions in the hepatopancreas for both groups were extensive, whereas that for oral administration was approximately 2.3 times greater than that for the intra‐sinus one. It was demonstrated that hepatopancreatic OTC may undergo significant first‐pass elimination with non‐linear kinetics.     

Effect of lactic acid on enrofloxacin pharmacokinetics in Eriocheir sinensis (Chinese mitten crab)

As a representative acidifier, lactic acid (LA) is widely used in the diets of aquatic animals. LA is the main supporter of energy metabolism and may be associated with drug metabolism. This study was designed to explore the pharmacokinetics of enrofloxacin (ENR) in Eriocheir sinensis (Chinese mitten crab) fed diets containing 0.1%, 0.2% and 0.3% LA (designated groups LA1, LA2 and LA3 respectively). The concentrations of ENR in the haemolymph, hepatopancreas and muscle were determined by HPLC after a single oral dose of 10 mg/kg. Our results showed that LA had a significant effect on the peak ENR concentrations in all the tissues (p < 0.05) by one‐way ANOVA analysis. There was a trend that C_max (peak concentration) of ENR was elevated with LA levels increasing up to 0.3% in haemolymph, hepatopancreas, muscle and T_max (time‐point of the peak concentration of the drug), t_1/2β (elimination half‐life) and AUC_(0‐∞) of ENR were shortened. Taken together, 0.3% LA might be effective in improving ENR pharmacokinetics in E. sinensis. Furthermore, it can be speculated that the enhanced biotransformation of ENR in the hepatopancreas mediated by LA is responsible for the differences in the pharmacokinetics of ENR in E. sinensis.     

土霉素在锯缘青蟹体内的药物代谢和消除规律

采用高效液相色谱法检测土霉素,研究土霉素口灌给药途径下在锯缘青蟹体内的药代动力学。锯缘青蟹口灌给药土霉素50 mg/kg后,其血浆、肌肉和肝胰脏中的药峰浓度分别为16.78±1.98 mg/L、9.39±2.12μg/g和32.12±6.12μg/g,达峰时间分别为4 h、8 h和4 h。血浆中土霉素浓度-时间关系曲线符合一级吸收的二室开放动力学模型。土霉素在锯缘青蟹体内分布广泛,其表观分布容积(Vd)为2.129 L/kg;分布半衰期(t1/2α)和消除半衰期(t1/2β)分别为3.200 h和47.856 h,总体清除率(CLs)为0.063 mL/(kg.h)。肌肉和肝胰脏中土霉素浓度与时间关系的药动学参数采用统计矩原理分析,其消除半衰期(t1/2 z)分别为60.145 h和71.009 h,总体清除率(CLz)分别为0.054 g/(kg.h)和0.037 g/(kg.h)。土霉素在精巢和卵巢中达峰时间分别为8 h和12 h,峰浓度分别为9.83μg/g和10.26μg/g。给药后24 d时,血浆、肌肉、肝胰脏、精巢和卵巢中土霉素含量都已低于0.10μg/g。土霉素在锯缘青蟹体内消除比较缓慢。     

盐酸沙拉沙星在凡纳滨对虾体内药动学与生物利用度

采用RP-HPLC法研究了在盐度33、水温（28.0±1.0）℃的自然海水中盐酸沙拉沙星单剂量围心腔注射（剂量10 mg·kg-1）和单次药饵投喂（剂量30 mg·kg-1）给药后在凡纳滨对虾（Litopenaeus vannamei）体内的药动学与生物利用度。围心腔注射给药后,血淋巴中药时曲线较适合用二室模型来拟合,而药饵投喂给药后血淋巴中药时曲线较适合采用一级吸收二室模型来拟合。药饵给药下盐酸沙拉沙星在凡纳滨对虾体内的生物利用度（F）为61.6%。药饵投喂给药下大量药物分布到了肝胰腺,肝胰腺血药峰浓度（Cmax）和AUC0-t分别是血淋巴的24.4倍和18.7倍,分别是肌肉的51.9倍和62.0倍;药物在肝胰腺和肌肉中消除都很快,分别在给药后5 d 和36 h低于0.1 mg·kg-1。由此可见,盐酸沙拉沙星药饵给药下吸收好,达峰值高和生物利用度好,且在肌肉和肝胰腺组织中消除快,是较为理想的防治对虾细菌性疾病的抗菌药物。     

伊维菌素在鲫体内的药代动力学

以0.4 mg/kg的给药剂量进行口灌和肌肉注射给药,研究伊维菌素(IVM)在鲫体内的药代动力学。两种给药方式下,鲫组织中的IVM药—时曲线大都呈现多峰现象。肌肉注射给药后,药动学统计矩参数为Cmax=0.445 mg/L、Tmax=48 h、t1/2z=524.2 h、MRT(0-∞)=788 h、AUC(0-∞)=289.2(mg/L).h;口灌给药后,药动学统计矩参数为Cmax=0.264 mg/L、Tmax=8 h、t1/2z=153.9h、MRT(0-∞)=269.78 h、AUC(0-∞)=83.77(mg/L).h。两种给药方式相比,口灌组鲫对药物的吸收和清除均较快,而肌肉注射组鲫各组织中的药物浓度高,AUC值也较大。两种给药方式下,IVM在鲫各组织中AUC(0-600)值呈现相同的排列顺序,由大到小分别为性腺、血液、肾脏、肝胰脏、肌肉。IVM在鲫性腺和肾脏中均具有一定的蓄积作用,其主要表现为药物浓度高,MRT值大,且清除率低于血药的清除率,其中卵巢的积蓄作用最为明显。25℃的水温条件下,肌肉注射给药后,鲫休药期应不低于25 d;口灌给药后,鲫的休药期应不低于15 d。休药期与水温条件和给药剂量有关,因此在养殖生产过程中的休药期要根据实际情况适当调整。     

恩诺沙星及其代谢产物在中华绒螯蟹血淋巴中的比较药代动力学

研究了不同水温(16℃、25℃)、不同给药剂量(10 mg/kg、20 mg/kg)和不同给药方式(肌注、口灌)等条件下,恩诺沙星及其代谢产物环丙沙星在中华绒螯蟹体内的药代动力学,比较了不同条件下药物在蟹血淋巴中的吸收、分布和代谢的差异。结果表明,恩诺沙星在蟹血淋巴中的药-时数据符合开放式二室模型。16℃时以10 mg/kg剂量肌注给药后,恩诺沙星在蟹血淋巴的主要药代动力学参数为:AUC96.818 mg/(L.h),Cmax6.54μg/mL,t1/2α0.851 h,t1/2β95.415 h;25℃时以10 mg/kg剂量肌注给药后,恩诺沙星的主要药代动力学参数为:AUC168.457 mg/(L.h),Cmax7.12μg/mL,t1/2α0.58h,t1/2β88.833 h;25℃时以20 mg/kg剂量肌注给药后,恩诺沙星的主要药代动力学参数为:AUC155.612 mg/(L.h),Cmax11.045μg/mL,t1/2α5.239h,t1/2β88.378 h;25℃时以10 mg/kg剂量口灌给药后,恩诺沙星的主要药代动力学参数为:AUC86.525 mg/(L.h),Cmax3.469μg/mL,t1/2α8.071h,t1/2β61.842 h。不同条件下,恩诺沙星在蟹血淋巴中的主要药代动力学参数差异较大。恩诺沙星的活性代谢产物环丙沙星在各种给药条件下的蟹血淋巴中均能检出,但含量均处于较低值,且药-时数据不能用房室模型拟合,表明恩诺沙星在蟹体内只有极少部分代谢为环丙沙星。     

鱼类恩诺沙星药残消除研究进展

恩诺沙星（enrofloxacin, ENR）是一种吸收分布快、血药浓度高、药效持久和生物利用度高的抗菌素,在鱼类疾病防治中广泛应用。然而,近年来,鱼类与养殖环境ENR药残事件对人类与生态的安全影响,已成为公众日益关注的焦点。本文在归纳鱼类ENR消除研究基础上,从ENR自身结构与性质,ENR与鱼类种类、发育阶段、组织差异、生理与病理状况、给药剂量与给药方式,以及温度、盐度、光照等环境因子关系,对鱼类ENR药残成因进行追溯分析。首次分析发现并提出底栖鱼类较其他水层鱼类易于形成ENR药残蓄积的假说,其可能与沉积环境有机质丰富,易于吸附ENR,底层黑暗环境无法光解ENR,底层鱼类从沉积环境吸收、富集ENR有关,建议对底层鱼类ENR休药期重新研究界定,对其ENR药残机制进行着重研究。首次提出基于选择突变窗理论的ENR大剂量给药模式,是引发当前鱼类与环境ENR药残主要根源。据此,提出基于ENR最小抑菌浓度的ENR减量给药方案,联合具有抗菌和促解毒功能的传统中草药,以达到ENR减量增效,降低ENR耐药性,促进ENR药残从养殖鱼体消除,缩短鱼类ENR休药期,降低养殖环境ENR药残的目的。同时,为减少鱼类ENR的环境来源,应结合进行环境ENR消除技术研究。本文可为养殖鱼类ENR科学用药与药残风险控制提供研究思路。     

Pharmacokinetics of enrofloxacin and its metabolite ciprofloxacin in Pacific white shrimp <Emphasis Type="Italic">Litopenaeus vannamei</Emphasis> after multiple-dose oral administration

The present study was designed to explore pharmacokinetics (PK) of enrofloxacin and its metabolite ciprofloxacin in Pacific white shrimp Litopenaeus vannamei after multiple-dose oral administration of enrofloxacin (30 mg/kg dose per 12 h and continuous feeding for 3 days). Enrofloxacin and ciprofloxacin concentrations in hemolymph, hepatopancreas, and muscle of the shrimp were simultaneously determined by high-performance liquid chromatography. PK parameters were analyzed based on statistical moment theory. Meanwhile, the relationship of pharmacokinetics/pharmacodynamics (PK/PD) was established based on drug concentration of hemolymph and in vitro antibacterial activity (MIC value). Results showed faster absorption of enrofloxacin in hemolymph (T_max?=?1 h) and muscles (T_max?=?1 h) than that in hepatopancreas (T_max?=?3 h) after the first oral administration. In multiple-dose oral administration, slight accumulation of enrofloxacin occurred in the hemolymph and hepatopancreas, while in the muscle, enrofloxacin concentration showed a significant decline following multiple administration. Tissue distribution of enrofloxacin and ciprofloxacin both followed the order hepatopancreas?>?hemolymph?>?muscle, with significantly higher ciprofloxacin concentration in hepatopancreas than in hemolymph (approximately 10-fold) and muscles (approximately 50-fold), indicating that the hepatopancreas is the main organ involved in metabolism of enrofloxacin in Pacific white shrimp. After multiple-dose administration, C_max/MIC and AUC_0–24/MIC values showed that the therapeutic regimen in this study could be remarkably effective in prevention and treatment of Vibrio infection in Pacific white shrimp.     

Pharmacokinetics of oxolinic acid in gilthead sea bream, Sparus aurata L.

This is the first study on the pharmacokinetic parameters of oxolinic acid (OA) in gilthead sea bream, Sparus aurata L. The kinetic profile of OA was studied after a single intravascular injection (20 mg kg⁻¹) in 100 g fish at 20 °C. The distribution half-life ( t _1/2α) and the elimination half-life ( t _1/2β) of the drug were found to be short (0.51 and 12.60 h, respectively). The drug penetration from the plasma to the tissues was adequate as the apparent volume of distribution of the drug at steady-state ( V _d(ss)) was found to be 2.11 L kg⁻¹. The mean residence time ( MRT ) of OA was short (14.25 h) and the total clearance rate ( Cl _T) of the drug was low (0.15 L kg⁻¹ h⁻¹). The bioavailability ( F %) of OA following oral administration (30 mg kg⁻¹) was also low (14%). Maximum values were observed for muscle at 0.5 h after injection, with levels declining as with subsequent sampling. At the first two time points (0.5 and 1 h) plasma levels of OA were higher than muscle, however, the reverse was evident for subsequent samples. Following oral administration, highest muscle levels were found at 16 h and, with the exception of the 24-h sampling, muscle OA concentrations were higher than plasma at all time points. The fast elimination of OA suggests short withdrawal times with reference to human consumption of treated fish.     

Antihypertensive effect of Narezushi, a fermented mackerel product, on spontaneously hypertensive rats

ABSTRACT:   During the fermentation of mackerel to narezushi , the concentration of peptides required to inhibit 50% of the ACE activity in the assay media (IC₅₀), as an index of the angiotensin  I-converting enzyme (ACE) inhibitory activity, was remarkably decreased with a rapid increase in peptide contents. Systolic blood pressure (SBP) in spontaneously hypertensive rats (SHR) decreased between 2 and 4 h after the single oral administration of greater than 10 mg peptide/kg narezushi extract, and recovered to the initial level by 8 h thereafter. The SBP decreased at seven successive daily doses of 10 mg/kg of narezushi extract and then recovered to the initial level 5 days after stopping a total of 10 daily administrations. The extract was administered to five-week-old SHR rats for 70 days and SBP decreased 21 days after starting and continued for 28 days after the end of administration. The peptide-rich fraction from narezushi extract had a powerful antihypertensive effect, whereas the other fraction had a similar, but weak effect.     

噁喹酸在欧洲鳗鲡体内的药代动力学及残留研究

在(25±1)℃水温条件下,分别采用口灌和浸浴的给药方式,以20 mg/kg的单剂量混饲口灌及5 mg/L的剂量浸浴18 h给予噁喹酸后,用高效液相色谱法测定血浆和肌肉中的药物浓度,研究了不同给药方式下噁喹酸在欧洲鳗鲡(Anguilla anguilla)体内的药代动力学特征.结果表明:欧洲鳗鲡口灌给药后,其血浆和肌肉...     

黄芩苷与甘草酸对恩诺沙星在异育银鲫体内代谢的影响

将黄芩苷(baicalin,BL)和甘草酸(glycyrrhizin,GZ)口灌异育银鲫(Carassius auratus gibelio),探讨其对恩诺沙星(enrofloxacin,ENR)在体内的代谢和肝微粒体细胞色素氧化酶CYP1A、CYP3A活性的影响。异育银鲫连续7 d分别口灌黄芩苷(100 mg/kg)和甘草酸(100 mg/kg),以口灌玉米油作为对照。末次给药24 h后每组随机取10尾腹腔注射恩诺沙星(10 mg/kg),采用单个动物连续采血,HPLC测定血浆恩诺沙星和其代谢产物环丙沙星(cipmfloxacin,CIP)浓度,分析药动学及其参数;同时每组选取6尾检测肝微粒体CYP1A和CYP3A活性。结果表明:(1)黄芩苷(BL)和甘草酸(GZ)对恩诺沙星的吸收有明显抑制作用,主要表现在恩诺沙星峰浓度(Cmax)降低,曲线下面积(AUC)减少;(2)口灌BL和GZ后,恩诺沙星及其代谢产物环丙沙星的消除半衰期(t1/2z)明显小于对照组(P<0.05),而总体清除率(CLz/F)则增大,说明黄芩苷和甘草酸促进了恩诺沙星和环丙沙星的消除;(3)口灌BL和GZ后,BL组和GZ组的Cmax-CIP/Cmax-ENR比值分别为1.48%、2.22%,对照为0.95%;BL组和GZ组的AUC0-t-CIP/AUC0-t-ENR比值分别为2.16%、1.76%,对照组为1.7%。综合分析代谢产物环丙沙星峰浓度、Cmax-CIP/Cmax-ENR和AUC0-t-CIP/AUC0-t-ENR比值可以得出,黄芩苷和甘草酸对恩诺沙星N-脱乙基具有诱导作用;(4)与对照组相比较,BL组和GZ组的7-乙氧基异吩唑酮-O-脱乙基酶(EROD,CYP1A标志酶)和红霉素-N-脱甲基酶(ERND,CYP3A标志酶)活性显著升高(P<0.05),说明黄芩苷和甘草酸对CYP1A和CYP3A都有诱导作用。结合以上结果,认为黄芩苷和甘草酸加速了恩诺沙星的消除和其代谢产物CIP的生成,很可能与诱导CYP1A和CYP3A活性有关。     

Kinetics of diarrhetic shellfish poisoning toxins,okadaic acid,dinophysistoxin-1, pectenotoxin-6 and yessotoxin in scallops <Emphasis Type="Italic">Patinopecten yessoensis</Emphasis>

ABSTRACT:   Four toxins, okadaic acid (OA), dinophysistoxin-1 (DTX1), pectenotoxin-6 (PTX6), and yessotoxin (YTX), all associated with diarrhetic shellfish poisoning (DSP), were administered via syringe to Scallops Patinopecten yessoensis and their distribution in the hepatopancreas, adductor muscle, and combined other tissues (mantle, gill, gonad) was analyzed by liquid chromatography-mass spectrometry. Toxins exclusively remained in the hepatopancreas irrespective of the injection site, adductor muscle or hepatopancreas. When injected into hepatopancreas, OA, DTX1, and YTX were metabolized to 7- O -palmitoylOA, 7- O -palmitoylDTX1 and 45-hydroxyyessotoxin (45OH-YTX), respectively. Such metabolic changes were insignificant when toxins were injected into the adductor muscle. The residual ratio for each toxin in the hepatopancreas was less than 20%. Mortalities of scallops treated with PTX6 were lower than those treated with other toxins.     

Effects of oestradiol-17β or 17α-methyltestosterone administration on gonadal differentiation of largemouth bass Micropterus salmoides (Lacepède)

Monosex populations can be a valuable management tool in culture of larger size largemouth bass (>400 g). In this study, we investigated the effective mode and duration of oestrogen and androgen administrations to produce monosex largemouth bass populations. The experiment consisted of nine treatments. In oral administration groups, we fed 40-day-old fry either 200 mg of an oestradiol-17β (E₂) kg⁻¹ diet or 60 mg of a 17α-methyltestosterone (MT) kg⁻¹ diet for 30, 45 or 60 days. In bath treatments, we immersed fry in a 1 mg MT L⁻¹ solution for 5 h a day on three or six occasions. For control treatment, we fed fry an ethanol-treated diet for 45 days. The frequency of females in the control group was 53.1%. Oral administration of E₂ at all durations resulted in slight increases in the frequency of females (59.8–70.5%). Both modes of androgen administration at all durations were ineffective in altering phenotypic sex. The experimental results of our study indicated that male differentiation passed the point of being completely and functionally influenced by exogenous oestrogens, while female differentiation had already taken place and was no longer responsive to exogenous androgens in 40-day-old (33.5 mm) largemouth bass fry.     

复方磺胺嘧啶口灌给药在拟穴青蟹(Scylla paramamosain)体内药动学和组织分布与消除

研究了水温为(27±1)℃、盐度为10条件下,单剂量(100 mg/kg)口灌给药复方磺胺嘧啶(磺胺嘧啶SD:甲氧苄啶TMP=5:1)后,SD和TMP在拟穴青蟹(Scylla paramamosain)体内的药动学以及在肌肉、肝胰腺和鳃组织中的分布和消除规律.结果显示,拟穴青蟹口灌复方磺胺嘧啶后,血淋巴中SD和TMP药物浓度-时间关系曲线均符合一级吸收二室模型,SD和TMP的峰浓度(Cmax)分别为49.56 mg/L和2.79 mg/L,药时曲线下面积(AUC)分别为1417.6 mg/L.h和82.7 mg/L·h;肝胰腺是SD和TMP峰浓度最高的组织,其Cmax分别为59.36 mg/kg和74.82 mg/kg.由此可见,大量TMP蓄积在肝胰腺中,进入血液循环的TMP很少.在鳃组织中,SD和TMP的Cmax分别为51.89 mg/kg和42.58 mg/kg,消除半衰期分别为23.28 h和25.29 h;鳃组织中药物浓度比较高,且消除速度较快,推测其在药物代谢中承担着消除功能.在肌肉中,SD和TMP的Cmax分别为44.95 mg/kg和10.09 mg/kg,消除半衰期分别为25.09 h和35.08 h.以0.1 mg/kg和0.05 mg/kg分别为SD和TMP的最高残留限量(MRL),95％置信区间,推算SD和TMP在拟穴青蟹肌肉中的理论休药期分别为290.6 h和302.8 h,在肝胰腺中分别为340.4 h和377.0 h.     

Pharmacokinetics of oxolinic acid in black tiger shrimp, Penaeus monodon Fabricius, and the effect of cooking on residues

This study examined the pharmacokinetics and bioavailability of oxolinic acid (OA) in black tiger shrimp Penaeus monodon Fabricius, in brackish water (salinity 10 g L^?1) at 28–29°C, after intra‐sinus (10 mg kg^?1) and oral (50 mg kg^?1) administration and also investigated the net changes of OA residues in the shrimp after cooking (boiling, baking and frying). The haemolymph concentrations of OA after intra‐sinus dosing were best described by a two‐compartment open model. The distribution and elimination half‐lives were 0.84 and 17.7 h respectively. The apparent volume of distribution at a steady state and the total body clearance were estimated to be 2061 mL kg^?1 and 90.1 mL kg^?1 h^?1 respectively. The bioavailability of OA after an oral administration was 7.9%. The peak haemolymph concentration, the time to peak haemolymph concentration and the elimination half‐life after oral administration were 4.20 μg mL^?1, 4 h and 19.8 h respectively. Oxolinic acid muscle and shell levels increased to a maximum (muscle 1.76 μg g^?1 and shell 8.17 μg g^?1) at 4 h post administration and then decreased with the elimination half‐life value of 20.2 and 21.9 h respectively. Residual OA in muscle and shell was reduced by 20–30% by each cooking procedure examined.     

恩诺沙星及其代谢产物环丙沙星在拟穴青蟹体内的药代动力学

采用高效液相色谱法,研究盐度33条件下恩诺沙星口灌和肌肉注射给药(剂量10 mg/kg)后,恩诺沙星及其代谢物环丙沙星在拟穴青蟹体内的药代动力学和组织分布。血淋巴和组织中药代动力学参数采用基于统计矩原理的非房室模型进行计算。恩诺沙星口灌和肌肉注射拟穴青蟹给药后,血药达峰快,分别为0.5 h和1 min,达峰浓度分别为12.90和31.86 μg/mL,曲线下面积(AUC)分别为216.1和816.8 μg/(mL·h)。恩诺沙星在拟穴青蟹组织中分布较广,口灌给药下肌肉和肝胰腺AUC分别为445.9和817.6 μg/(g·h),肌肉注射给药下的AUC分别为554.7和2 573.7 μg/(g·h)。与其它水产动物相比,恩诺沙星在拟穴青蟹体内消除速度为中等水平,口灌和肌肉注射恩诺沙星后血药消除半衰期(t_1/2z)分别为26.45和57.02 h,总体清除率(CL_z)分别为0.054和0.012 L/(h·kg)。恩诺沙星在拟穴青蟹体内代谢生成环丙沙星的量较少,口灌给药下血淋巴、肌肉和肝胰腺的AUC_CIP/AUC_ENR分别为6.66%、3.66%和4.78%,肌肉注射给药下,其相应值分别为4.16%、7.24%和1.48%,在拟穴青蟹体内起药效作用仍是以恩诺沙星为主。以C_max/MIC、AUC_0-24/MIC评价恩诺沙星在青蟹体内的药效作用,建议给拟穴青蟹以10 mg/kg剂量每隔24小时投喂一次恩诺沙星,对弧菌引起的细菌性疾病具有较好的防治效果。