四环素类抗菌药物在吉富罗非鱼体内的代谢动力学研究

给吉富罗非鱼一次灌服50mg/kg剂量的四环素和土霉素浑浊液,研究四环素和土霉素在其肌肉、肝脏和血液中的残留与消除规律。12h后四环素、土霉素在肌肉、肝脏和血液中含量分别达最高,四环素含量分别为0.920mg/kg,2 703mg/kg,1 225μg/mL;土霉素含量分别为0 860,2 188mg/kg和1 075μg/mL。鱼肉中四环素的分布半衰期和消除半衰期分别为8 593,23 50h;土霉素的分布半衰期和消除半衰期分别为8 261,22 979h。216h后,鱼肉中四环素和土霉素均低于0 1mg/kg。     

恩诺沙星在日本鳗鲡体内残留消除规律研究

采用高效液相色谱法检测日本鳗鲡肌肉、血清、肠、鳃和肝脏组织中恩诺沙星及其代谢物环丙沙星的残留。方法的日内和日间变异系数分别为1.86%和2.53%,标准添加回收率为(95±6)%;最低测量限为1.0μg/kg。用现场试验方法研究恩诺沙星在鳗鱼体内的代谢残留规律。对约50 g鳗鱼按9 mg/kg鱼体重每天给药2次,连续投喂7 d。给药期间鳗鱼体内的药物含量呈锯齿状上升,停药60 d后鳗鱼肠、鳃和肝脏组织中药物即下降至1~5μg/kg。肌肉和血清中药物残留到90 d,分别消除至3μg/kg和4μg/kg。所测组织的药物残留至停药120 d后降到检测限以下。故鳗鱼的停药期不应低于120 d。     

盐酸氯苯胍在眼斑拟石首鱼体内的药代动力学和残留消除规律研究

在水温(28±2)℃、盐度28条件下,采用30mg/kg的剂量口灌法,用HPLC-MS/MS检测研究了盐酸氯苯胍在体质量为(350.15±5.18)g的眼斑拟石首鱼体内的药代动力学和残留消除规律。结果显示,单剂量口灌给药后,眼斑拟石首鱼血浆中盐酸氯苯胍的药时数据符合一级吸收二室模型,药物在血浆中的达峰时间、血药质量浓度峰值、药时曲线下面积和消除半衰期分别为2.39h、958.78μg/L、33 247.57μg/(L·h)和19.24h;盐酸氯苯胍在肌肉、肝脏和肾脏的血药含量峰值分别为156.72、227.68μg/kg和553.44μg/kg,达峰时间分别为2.0、1.5、2.0h;药时曲线下面积分别4664.04、4897.74、17 228.19μg/(kg·h);消除半衰期分别为19.68、24.33、22.81h。按30mg/kg剂量连续5d口灌给药后,鱼血浆、肌肉、肝脏、肾脏中的药物消除半衰期(t1/2)分别为24.46、35.39、39.60、33.94h。若以10μg/kg为最高残留限量,肌肉作为食用靶组织,在本试验条件下,建议休药期不少于7d。     

3种抗菌药物在大菱鲆体内的残留消除规律比较

应用反相液相色谱法对氟苯尼考、土霉素和磺胺间甲氧嘧啶3种抗菌药物在大菱鲆体内的残留消除规律进行了比较研究.结果表明,氟苯尼考在肌肉、血液、皮肤、肝脏和肾脏中的消除半衰期(t1/2)为24～30h左右,土霉素在各组织中t1/2为2～3d,而磺胺间甲氧嘧啶在肌肉、血液和皮肤中的t1/2与氟苯尼考接近,在肝脏和肾脏中的t1/2与土霉素相似.本试验条件下,氟苯尼考、土霉素和磺胺间甲氧嘧啶3种抗菌药物在大菱鲆肌肉组织中降低到最高残留限量0.2、0.1和0.1μg/g下所需要的理论时间为10、20和15d,本试验的水温为23±2℃,考虑到温度为影响药物代谢和残留的最主要环境因素,建议氟苯尼考、土霉素和磺胺间甲氧嘧啶在大菱鲆体内的休药期为250、500和375度日.     

恩诺沙星在养殖大菱鲆体内的残留及消除规律

在11～12 ℃水温条件下,对大菱鲆Scophthalmus maximus连续口服恩诺沙星7 d后肌肉、血清和肝脏组织中该药物及其代谢产物环丙沙星的残留及消除规律进行了研究.大菱鲆肌肉、血清和肝脏中残留的恩诺沙星药物用二氯甲烷提取,在不同的时间点利用反相高效液相色谱荧光检测法检测药物浓度,最低检测限为0.01 μg/ml,平均回收率为75%～87%.研究结果表明,恩诺沙星按一级动力学过程从体内消除,在3种组织中消除速率不同,在肌肉、血清和肝脏中的消除曲线方程分别为C=1.560e-0.0310 t、C=1.147e-0.018 9 t和C=0.920e-0.027 1 t;恩诺沙星在3种组织中的消除半衰期较长,分别为22.53、36.67和25.57 d.在给药后的第94天,肌肉组织中的恩诺沙星浓度持续保持0.168 μg/g,尽管NY5070-2002无公害水产食品中恩诺沙星和环丙沙星的残留限量MRL(Maximum residue limit)要求为0.05 μg/g,但本试验数据提示,大菱鲆肌肉组织中残留的恩诺沙星和环丙沙星超过了标准,建议合理的休药期应不少于120 d.     

诺氟沙星在大黄鱼体内的药代动力学及残留研究

在试验水温(22±2)℃时,按10 mg.kg-1的剂量给大黄鱼单次口服诺氟沙星后,用高效液相色谱法测定血浆和组织中的药物浓度,研究了诺氟沙星在大黄鱼体内的代谢及消除。结果表明血药时间数据符合一级吸收二室开放模型,吸收分布迅速,但消除缓慢,半衰期(T1/2 Ka、T1/2α、T1/2β)分别为0.703 0、2.092 6、154.326 5 h,最大血药浓度为0.886 4μg.mL-1,达峰时间为2.091 4 h,药时曲线下面积(AUC)为97.803 8μg.h.mL-1。组织中肝脏的药物浓度最高,在测定的时间里各组织的药物浓度高于血浆。药物消除速度依次为:肾脏、肝脏、肌肉,消除半衰期分别为135.88、173.25、223.55 h,肌肉作为可食性组织,且消除最慢,因此选取肌肉组织作为残留检测的靶组织,以50μg.kg-1为最高残留限量,因此在本试验条件下,建议休药期不低于23 d;在治疗大黄鱼细菌性疾病时,以诺氟沙星10 mg.kg-1剂量给药,一般1 d 1次,连用2~3 d。     

单次投喂乳酸诺氟沙星在鳜鱼体内的代谢消除规律

水温(28±2)℃时,按20mg/kg的剂量给平均体质量(500±10)g的鳜鱼单次口服乳酸诺氟沙星,服药后0.5、1、2、3、4、6、8、12、24、48、72、96h,分别测定鳜鱼血浆、肌肉、肝脏和肾脏中的药物含量,采用非房室模型分析药物在鳜鱼体内的代谢消除规律。结果显示,乳酸诺氟沙星在鳜鱼血浆、肌肉、肝脏、肾脏中的达峰时间分别为4.333、6、3、5h,达峰质量浓度分别为3.625、2.39、33.089、19.375mg/L,各组织中肝脏吸收的药物含量最高,其次是肾脏、血浆和肌肉;乳酸诺氟沙星在鳜鱼血浆、肌肉、肝脏、肾脏中的消除半衰期分别为42.589、131.652、16.830、30.558h,药物在肝脏中消除速度最快,而在肌肉中消除最慢。以肌肉中药物残留限量为50μg/kg计,建议单次投喂乳酸诺氟沙星的休药期不低于24d。     

恩诺沙星及其代谢产物在吉富罗非鱼、中国对虾体内的残留规律研究

模拟水产养殖实际,每天以剂量为50μg/g(鱼体重)的恩诺沙星分别给吉富罗非鱼、中国对虾投喂药饵,周期为7d,研究恩诺沙星在罗非鱼和对虾体内的残留与代谢规律,制定停药期。实验结果发现,恩诺沙星在鱼、虾体内均代谢为环丙沙星。在停药的"零"时,鱼肌肉、肝脏和血液中恩诺沙星的含量分别为(3 61±1 02)μg/g、(5 96±2 12)μg/g、(1 25±0 23)μg/mL,消除半衰期分别为15 61,16 83,17 19h。鱼肌肉中代谢物环丙沙星的最高含量为(0 22±0 06)μg/g,消除半衰期67 3h;中国对虾体内恩诺沙星与环丙沙星的最高含量分别为(1 68±0 41)μg/g、(0 066±0 03)μg/g,消除半衰期分别为27 9,33 6h。在本实验条件下,建议罗非鱼的停药期为22d,中国对虾为12d。     

3种药物在甲鱼体内的残留研究

将呋喃唑酮、磺胺嘧啶和诺氟沙星各以3种水平分别混入饲料中投喂甲鱼（中华鳖Trionyx sinensis)，投药饵时间分别为7d和14d。停药后24、72、120和240h分别取血液、肝、肾和肌肉测定药物残留量。结果表明，呋喃唑酮的吸收量甚微，4种样品中均未检出残留，说明该药只适用于肠道疾病的防治；磺胺嘧啶在4种样品中均可检出，在停药后24h，血液中含量最高，然后迅速降低，72h降至最低，240h则不能检出；诺氟沙星的药物残留变化状况与磺胺嘧啶相似。残留排除速度以肌肉中最慢，以停药24h残留量为标准，停药120h磺胺嘧啶残留率为76．8％（1．65－2．37μg/kg），诺氟沙星为46％（0．81－0．93μg/kg）；停药240h则分别为25％（0．63－1．11μg/kg）和24．2％（0．35－0．44μg/kg）。血液、肝、肾和肌肉中的药物残留水平随给药量的增加而增加，给药时间的长短对血液中的药物浓度影响不大，但在肝、肾和肌肉中的药物残留则随给药时间的加长而显著增加（P＜0．05）。建议饲喂磺胺嘧啶或诺氟沙星的甲鱼应在停药10d后上市。     

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。     

Pharmacokinetics and bioavailability of oxytetracycline in vannamei shrimp (Penaeus vannamei) and the effect of processing on the residues in muscle and shell

The present study examined the pharmacokinetics and bioavailability of oxytetracycline (OTC) in vannamei shrimp (Penaeus vannamei) after intra-sinus (10 mg/kg) and oral (10 and 50 mg/kg) administration and also investigated the net changes of OTC residues in the shrimp after the thermal, acid and alkaline processing methods. The hemolymph concentrations of OTC after intra-sinus dosing were best described by a two-compartment open model. The oral bioavailability was found to be 48.2 and 43.6% at doses of 10 and 50 mg OTC/kg, respectively. The peak hemolymph concentrations after 10 and 50 mg OTC/kg doses were 3.37 and 17.4 μg/ml; the times to peak hemolymph concentrations were 7 and 10 h. The elimination half-lives were found to be 15.0 and 11.5 h for the low and high dose, respectively. The residual OTC was rapidly eliminated from muscle with the elimination half-life value of 19.4 and 15.4 h, respectively, for the groups treated with doses of 10 and 50 mg/kg. The residual OTC levels in the muscle fell below the MRL (0.2 μg/g) at 72 and 96-h post-dosing at dose levels of 10 or 50 mg/kg, respectively. Residual OTC levels in muscle and shell were approximately 20–50% lower in the thermal treatment such as boiling, baking and frying. By the acid treatment, OTC residues were reduced to >80%, while those were reduced to around 30% by alkaline treatment.     

土霉素在黑鲷体内的药物代谢动力学研究

首次报道了黑鲷口服土霉素的药物代谢动力学特征，用高效液相色谱法测定组织中的药物含量，药物在肌肉，血液，肝脏中的平均回归率分别为８５.61%,85.38%,82.005,该方法的检测限可达0.01μg/g，黑鲷１次口服剂量为７５mg/kg的土壤素后，其血液药物浓度－时间数据符合一室开放动力学模型，吸收速率常数（ka)为０.296/h，达峰时间（Ｔamx)为１０.635h,峰浓度（Ｃmax)为１.398μg/ml, 分布半衰期（Ｔ１／２a）为２.339h ,消除半衰期(T1/20β）为46.663h，药时曲线下面积（ＡＵＣ）为１１0.25mg/L.h，黑绸口服药物０.5h后在血液，肥肉，肝脏，肾脏４种组织中就可以检测到药物的存在，药物在１６h的采样点浓度达最高，分别为1.68μg/ml,1.68,2.52,6.77μg/g。     

呋喃唑酮代谢物AOZ在斑点叉尾(鲴)体内组织分布与消除规律研究

研究了在池塘网箱养殖模式下,平均水温为30.6℃,以100 mg/kg鱼体重的剂量投饲斑点叉尾鲴(Ietalurus punetaus)苗种(95±20.9)g含呋喃唑酮的药饵,连续5d,每天2次.采用高效液相色谱串联质谱(HPLC-ESI/MS/MS)法分析了呋喃唑酮主要代谢产物3-氨基-2-噁唑烷酮(3-amina...     

Pharmacokinetics and tissue distribution of oxytetracycline in carp, Cyprinus carpio L., following different routes of administration

Abstract. The objective of this pharmacokinetic study was to investigate absorption, distribution, elimination and bioavailability of oxytetracycline (OTC) in carp, Cyprinus carpio L ., after different routes of administration, OTC was administered intravenously (i.v.), intramuscularly (i.m.) and orally at 60 mg/kg body weight. OTC levels were determined in plasma and several tissues. Analysis of the plasma drug concentration-time curves following i.v. OTC injection revealed three distinct phases. A three-compartment open model was used to derive pharmacokinetic parameters. Compared to mammals, a very extended final elimination half-life was observed (139.8±38.1 h). Following i.m. OTC administration, C_max was 56.8±10.9μg OTC/ml at 14 h post-injection. The Vd area was 2.1 ± 0.66 1/kg. Extreme differences were observed with respect to bioavailability following i.m. and oral administration; approximately 80 and 0.6%, respectively. Following i.m. injection tissue OTC determinations revealed that the drug was accumulating in pronephros, bone tissue and scales. After 21 days the OTC concentrations were 2.9±0.8, 5.2±0.3 and 4.7±3.1 μg/ ml, respectively. In tissue samples from the dorsal region (muscle), including the injection site, OTC could not be demonstrated at that time. The pharmacokinetic data are discussed in relation to the susceptibility of the immune system of fish for modulation.     

盐酸土霉素在奥尼罗非鱼体内的药代动力学及残留研究

在水温(25±2)℃条件下,以15 mg/kg鱼体重的剂量给奥尼罗非鱼单次口灌盐酸土霉素,采用高效液相色谱法测定血浆和肌肉组织中的药物浓度,研究盐酸土霉素在奥尼罗非鱼体内的代谢及消除规律。结果显示:血药时间数据符合一级吸收二室开放模型,半衰期(T1/2Ka、T1/2α、T1/2β)分别为4.79、4.10、45.20 h,最大血药浓度为1.50μg/m L,达峰时间为7.30 h,药时曲线下面积(AUC)为42.35μg·h/m L。肌肉作为可食性组织,选取肌肉组织作为残留检测的靶组织,以0.1 mg/kg为最高残留限量,在本试验条件下,建议休药期不低于10 d。     

Pharmacokinetics and tissue distribution of oxytetracycline in sea bass, Dicentrarchus labrax, at two water temperatures

A pharmacokinetic study of oxytetracycline (OTC) following an intravascular administration (40 mg/kg) was carried out in sea bass, Dicentrarchus labrax (110 g), at 13.5 and 22 °C water temperature. Blood, muscle and liver samples were taken at 1, 2, 4, 8, 16, 32, 64 and 128 h post-injection. The plasma data were conformed to a two-compartment model. The kinetic profile of the drug was found to be temperature dependent. The absorption half-life (t_1/2) of OTC was 0.98 and 0.192 h at 13.5 and 22 °C, respectively, whereas the elimination half-time (t_1/2β) of the drug was 69 h at 13.5 °C and 9.65 h at 22 °C. The apparent volume of distribution of the drug at steady state [V_d(ss)] was 5.62 l/kg at 13.5 °C and 2.59 l/kg at 22 °C. The mean residence time (MRT) of OTC was found to be 37.7 h at 22 °C and 71 h at 13.5 °C. The total clearance of the drug (CL_T) was calculated to be 73.5 and 68.7 ml/kg/h at 13.5 and 22 °C, respectively.

Liver levels indicated higher OTC values than respective muscle levels at all time points and for both temperatures. The elimination of OTC from tissues tested was faster at the high temperature, whereas the drug was eliminated faster from liver compared to muscle when comparisons are made at the same temperature.     

Oxytetracycline (OTC) accumulation and elimination in hemolymph, muscle and hepatopancreas of white shrimp Litopenaeus vannamei following an OTC-feed therapeutic treatment

The white shrimp, Litopenaeus vannamei, has become a very important species for the development of shrimp aquaculture in Northwest Mexico. However, viral and bacterial diseases are considered a major threat to the development of this industry. In the present study a trial was conducted to evaluate the tissue distribution, maximum concentration, and elimination of the widely used antibiotic oxytetracycline (OTC) in L. vannamei using indoor tanks under laboratory-controlled conditions. OTC was given to shrimp simulating a therapeutic treatment through medicated feed for 14 days followed by a period of feeding without antibiotic for another 14 days to evaluate the elimination pattern. Samples of hemolymph, muscle, and hepatopancreas were taken from medicated animals every two days for 28 days. All tissues were removed and frozen immediately in liquid nitrogen. OTC levels were analyzed by High Performance Liquid Chromatography (HPLC). Results showed an important OTC increase during consumption of medicated feed in all examined tissues. OTC maximum concentrations were 33.54 ± 11.19, 194.37 ± 16.11, and 18.79 ± 5.87 µg g^− 1 for muscle, hepatopancreas and hemolymph, respectively. Although the highest OTC level was found in the hepatopancreas, it required only two days after the start of dosing to reach this value, whereas the maximum OTC for muscle and hemolymph was detected after eight days of dosing. Ten days after the cessation of medicated feeding, the drug content in the shrimp tail muscle was under the detectable limit for the method (0.01 µg g^− 1 of OTC).     

Tissue distribution and depletion of sarafloxacin hydrochloride after in feed administration in gilthead seabream (Sparus aurata L.)

Tissue distribution and depletion of sarafloxacin was studied in gilthead seabream, under experimental field conditions at 25 and 18 °C, after in-feed administration of sarafloxacin hydrochloride for 5 days (10 mg/kg body weight/day). Ten fish per sampling point were examined during and after treatment. Muscle plus skin (n=10), liver, kidney and vertebra (pooled) were collected and analyzed by HPLC. Sarafloxacin concentrations in these tissues increased during the medication period, and then decreased rapidly. The highest sarafloxacin concentrations were recorded in liver (335.2 and 49.8 μg/g at 25 and 18 °C, respectively). In muscle plus skin, sarafloxacin concentrations were 193.0 and 42.0 μg/kg at 25 and 18 °C, respectively. Sarafloxacin residues were eliminated rapidly; at 36 h post treatment, the levels in muscle plus skin were 10.2 and 8.5 μg/kg at 25 and 18 °C, respectively. Elimination half-lives (t_1/2) were 17.8 and 32.5 h at 25 and 18 °C, respectively. Withdrawal period for the Maximum Residue Limit (MRL) of 30 μg/kg sarafloxacin in muscle plus skin (95% tolerance limit) at 25 °C was 42.2 h. The slow elimination from vertebra, relative to other tissues, suggests that vertebra behaves as a reservoir in gilthead seabream.     

Oxytetracycline Residue in Hybrid Striped Bass Muscle

Hybrid striped bass ( Morose saxatilis male × M. chrysops female) were injected with 25 and 50 mg oxytetracycline (OTC) per kg of fish. Rate of elimination of OTC from muscle tissue and inhibition of bacteria by muscle injected with OTC were studied. OTC residue in muscle of fish injected with 50 mg OTC/kg fish was much higher (P < 0.01) than that in fish injected with 25 mg/kg and took a longer time to clear from the muscle. In fish injected at 25 mg OTC/kg of fish, OTC was completely eliminated from muscle in 24 d; the rate of elimination constant (β) was 0.278/day and the half-life (t_1/2) 2.5 d. In fish injected at 50 mg OTC/kg of fish, the OTC was not depleted in fish muscle until 32 d after injection; the rate of elimination constant 13 was 0.265/day and the half-life was 2.6 d. No statistical difference was found in muscle OTC residue between male and female fish. Size of fish (16.5 to 21.5 cm and 21.6 to 25.5 cm) made little difference in OTC residue in muscle. Muscle removed from fish injected with 25 mg/kg OTC 12 d after injection inhibited the growth of Vibrio anguillarum, V. ordalii and Aeromonas hydrophila in cultures.