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。     

Kinetic analysis of oxytetracycline residues in Chinese mitten crab,Eriocheir sinensis,muscle following intramuscular administration

Crab culture is a very important economic industry in China. An epidemic of tremor disease of Chinese mitten crabs, Eriocheir sinensis, has become a serious problem in recent years. A spiroplasm has been proved to be the causative agent of this disease. Oxytetracycline (OTC) is used widely in aquaculture and was confirmed to be very effective against this pathogen. In this study, the distribution and depletion patterns of OTC in crab muscle were evaluated following single intramuscular doses of 2, 8 and 40 mg kg^?1 body weight. OTC was detected with a validated HPLC method. Concentration–time profiles were well described by a three‐compartment model with first‐order absorption after a single dose of 8 and 40 mg kg^?1. For comparison, a non‐compartment model was employed. A withdrawal time of 48.29 and 55.92 days was suggested prior to consumption after receiving 8 and 40 mg kg^?1. A recommended therapeutic dose of OTC in theory was calculated to be 36.37 mg kg^?1. OTC was distributed well throughout the body. The elimination of OTC in muscle was slower compared with fish and other crustaceans. A dose of 40 mg kg^?1 is suggested for practical use.     

土霉素及镉污染对土壤呼吸及酶活性的影响

随着饲料工业以及畜禽养殖业的规模化发展,抗生素和重金属在土壤环境中同时存在的几率不断增大。为了分析抗生素和重金属对土壤微生物生态系统的影响,以土霉素(OTC)与镉(Cd)为污染物,采用室内培养法,研究了土霉素(OTC)与镉(Cd)单一处理及复合污染对土壤呼吸和酶活性的影响。结果表明,10mg/kg重金属镉单独污染对土壤微生物呼吸表现为先抑制后激活作用,且显著抑制了土壤蔗糖酶、脲酶、磷酸酶活性,对3种酶活性平均抑制率从大到小依次为:蔗糖酶磷酸酶脲酶;1mg/kg土霉素显著激活土壤微生物呼吸,50和200mg/kg土霉素对土壤微生物呼吸的影响呈现出先抑制后激活的规律。各处理浓度下的土霉素对蔗糖酶和脲酶活性均主要表现为抑制作用,对磷酸酶活性的影响呈现出一定的波动性;当土霉素的浓度为1和200mg/kg时,其与10mg/kg镉的复合污染对土壤微生物呼吸及3种酶活性的影响主要为拮抗作用,但当土霉素的浓度为50mg/kg时,与10mg/kg镉的复合污染对土壤微生物呼吸及3种酶活性的影响则主要为协同作用。微生物呼吸对土霉素与镉胁迫更为敏感,最高抑制率和激活率分别可达98.98%和300.82%,土壤酶活性受土霉素和镉污染的影响要弱于它们对土壤微生物呼吸的影响。     

土霉素在土壤中的垂直迁移及其影响因素研究

采用土柱淋溶法,研究了土霉素在土壤中的垂直迁移特性,探讨了不同土壤类型、淋溶体积、淋溶液pH值、施药量等因素对土霉素在土壤中淋溶迁移的影响。结果表明,在红壤、黑钙土、赤红壤3种不同类型的土样中,土霉素的迁移深度为：赤红壤〉红壤〉黑钙土;土霉素主要富集在土壤表层,其含量随土壤深度增加而明显降低;同一深度的土壤中土霉素含量随着淋溶液体积的增加而增大,随pH值增大而减小;土霉素在土层中的含量分布、淋溶深度与其施药量均呈正相关;当淋溶液中含有一定量的土霉素溶液时,土霉素在土壤中的迁移深度明显增加。     

Residues from long-acting antimicrobial preparations in injection sites in cattle

Objective To investigate tissue residues of two longacting oxytetracycline (OTC) preparations in cattle.
Design A randomised drug residue trial.  

Animals

Two hundred and forty beef cattle in 24 groups of ten.
Procedure Two blind-coded 200 mg/mL OTC preparations were used in five treatment regimens of various combinations of injection sites (from one to five) and administrations (one or two). Five cattle from each group were slaughtered at 21, 30 and 60 days after injection and the injection site, urine, kidney and diaphragm muscle analysed for residues.
Results The OTC concentration exceeded the maximum residue limit in kidney in animals slaughtered 21 days after treatment, which is the prescribed withholding period. Concentration at the injection site was much greater than the maximum residue limit 30 days post-treatment, but not 45 days post-treatment. The residue was smaller when OTC had been injected in multiple sites. There was no difference between the two OTC preparations.
Conclusion A review of the maximum injection volume, site of injection and the withholding period is needed for long-acting OTC formulations.     

The Effects of the Method of Calculation on the Evaluation of the Pharmacokinetic Parameters of Oxytetracycline After Intravenous Administration to Calves

Errecalde, J.O., Mestorino, N. and Mariño, E.L., 1997. The effects of the method of calculation on the evaluation of the pharmacokinetic parameters of oxytetracycline after intravenous administration to calves. Veterinary Research Communications, 21 (4), 273-281The aim of this study was to assess the differences in the values of the pharmacokinetic parameters attributable to the use of either linear or nonlinear regression analysis and to find the effect of weighting schemes on these differences. Six calves received 20 mg/kg oxytetracycline i.v. Blood samples were drawn during 72 h. The assay of the drug was performed microbiologically. A bicompartmental pharmacokinetic model was used, kinetic analysis being carried out by linear regression (LR) and by weighted least-squares nonlinear regression (WLSNLR). Statistical analysis included a test for normality, the Kruskall-Wallis test and ANOVA with log transformation.The A0, and B0 did not show any statistically significant differences attributable to the mathematical method used. On the other hand, the statistically significant differences in the values found using the Kruskall-Wallis test and ANOVA with log transformation could be attributed to the different methods employed. ANOVA with log transformation determined statistically significant differences between the parameters obtained by linear analysis and those obtained by WLSNLR when the weighting (w) was 1. When weights were 1/x, 1/x2 or 1/ x, no statistically significant differences were found. The optimal weighting scheme was w = 1/x2 because of a more homogeneous scatter and random distribution of residuals about the abcissa axis in a plot of weighted residuals in the ordinate versus time in the abcissa. It was concluded that the use of these different procedures can give major variations in the apparent value of , the most important pharmacokinetic parameter. The correct selection of the weighting procedure is therefore fundamental in obtaining the best estimate of this pharmacokinetic parameter in WLSNLR.     

Study on Optimizations of Oxytetracycline Residues Detection Method in Milk and its Clinical Elimination

Here an improved HPLC-PAD method was developed and demonstrated suitable for studying the clinical residue elimination of oxytetracycline in milk from postpartum cows with uterine diseases after intrauterine treatment with oxytetracycline.In this study, 0.1 mol/L Na₂EDTA-Mcllvaine buffer solution was used to extract oxytetracycline from milk, n-hexane for degreasing, and a 3 CC Oasis HLB solid-phase extraction column for purification and concentration.A reversed phase chromatographic column Symmetry Shield RP C18 (250 mm×4.6 mm, 5 μm) with acetonitrile and 0.048% phosphoric acid solution (pH 2.5) as mobile phase by gradient eluting was applied to as the chromatographic separation condition.The results showed that the retention time of oxytetracycline was 6.5 min with a symmetrical and sharp peak, which was well separated from the impurity in the milk sample.Oxytetracycline standard solutions within the concentrations ranging from 5 to 2 000 μg/kg, had a good linearity between peak areas and the concentrations, R²=0.9999.The recoveries of oxytetracycline at three levels of 10, 20, 100 μg/kg were 87.9%, 90.5% and 87.8%, respectively, with the coefficient of variation ranged from 2.2% to 5.8% in intra-day and 4.0% to 5.1% in inter-day.The LOD was 5 μg/kg and the LOQ was 10 μg/kg.All of those parameters suggested that the optimized method was suitable for the study on the clinical residue elimination of oxytetracycline.29 postpartum cows with uterus disease were randomly divided into four different groups in terms of dosage, 2, 3, 4 and 5 g, and treated with oxytetracycline by intrauterine infusion administration, and the residues of oxytetracycline in milk were detected to study its clinical residue elimination.The results showed the oxytetracycline in milk fell to the MRL during 72 h after treatment at 4 g and below dose group.However, in 5 g dose group, residue levels of oxytetracycline in milk were above the MRL at 72 h after treatment.Therefore, 5 g and the higher were not recommended for intrauterine infusion administration.     

Kinetics and isotherms of oxytetracycline adsorption on β‐cyclodextrin/carboxymethylcellulose hydrogel films

Oxytetracycline (OTC), widely used as an antibiotic substance in aquaculture, has an adverse effect on environmental and public health. The aim of this paper was to demonstrate that OTC can be removed by hydrogel films composed of β‐cyclodextrin/carboxymethylcellulose (β‐CD/CMC) with esterification‐crosslink method. Oxytetracycline adsorption experiments were performed with an initial pH of 1–12 and an initial concentration of 10–500 mg/L. The experimental data were fitted with Langmuir and Freundlich isotherms and compared using linear and nonlinear models. The experimental results indicate that OTC's adsorption capacity depends on the active β‐cyclodextrin content. The optimal pH was around 8.     

紫外分光光度法测定长效土霉素注射液含量方法的建立

以0.01 mol/L盐酸溶液为参比液,采用紫外分光光度法在268 nm波长处测定长效土霉素注射液中土霉素的含量.结果表明,土霉素在5 μg/mL～30 μg/mL浓度范围内,其吸光度与浓度呈良好的线性关系,相关系数r=0.999 9,平均回收率为99.34%,变异系数为0.46%(n=6).该方法操作简便、快速、结果准确,适于作为生产企业中间产品的质量控制方法.