排序方式： 共有96条查询结果，搜索用时 765 毫秒
71.
Damrongsak Faroongsarng Sommai Chiayvareesajja Ausa Chandumpai Yongyuth Theapparat 《Aquaculture Research》2009,41(1):143-152
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. 相似文献
72.
Shigeru Hisada Kenjiro Tsubota Kenji Inoue Hisaharu Yamada Takanori Ikeda Frank D. Sistare 《Journal of toxicologic pathology》2022,35(1):53
The pharmacokinetic endpoint of a 25-fold increase in human exposure is one of the specified criteria for high-dose selection for 2-year carcinogenicity studies in rodents according to ICH S1C(R2). However, this criterion is not universally accepted for 6-month carcinogenicity tests in rasH2-Tg mice. To evaluate an appropriate multiple for rasH2-Tg mice, we evaluated data for 53 compounds across five categories of rasH2-Tg mouse-positive [(1) genotoxic and (2) non-genotoxic] carcinogens and rasH2-Tg mouse-negative [(3) non-genotoxic carcinogens with clear or uncertain human relevance; (4) non-genotoxic rodent-specific carcinogens; and (5) non-carcinogens], and surveyed their tumorigenic activities and high doses in rasH2-Tg mice and 2-year rodent models. Our survey indicated that area under the curve (AUC) margins (AMs) or body surface area-adjusted dose ratios (DRs) of tumorigenesis in rasH2-Tg mice to the maximum recommended human dose (MRHD) were 0.05- to 5.2-fold in 6 category (1) compounds with small differences between models and 0.2- to 47-fold in 7 category (2) including three 2-year rat study-negative compounds. Among all 53 compounds, including 40 compounds of the rasH2-Tg mouse-negative category (3), (4), and (5), no histopathologic risk factors for rodent neoplasia were induced only at doses above 50-fold AM or DR in rasH2-Tg mice except for two compounds, which induced hyperplasia and had no relationship with the tumors observed in the rasH2-Tg mouse or 2-year rodent studies. From the results of these surveys, we confirmed that exceeding a high dose level of 50-fold AM in rasH2-Tg mouse carcinogenicity studies does not appear to be of value. 相似文献
73.
Tetsuro KURAMAE Shingo ISHIKAWA Aki KONO Seiji HOBO 《The Journal of veterinary medical science / the Japanese Society of Veterinary Science》2022,84(3):400
This study analyzed the pharmacokinetics of orbifloxacin (OBFX) in plasma, and its migration and retention in epithelial lining fluid (ELF) and alveolar cells within the bronchoalveolar lavage fluid (BALF). Four healthy calves received a single dose of OBFX (5.0 mg/kg) intramuscularly. Post-administration OBFX dynamics were in accordance with a non-compartment model, including the absorption phase. The maximum concentration (Cmax) of plasma OBFX was 2.2 ± 0.1 μg/ml at 2.3 ± 0.5 hr post administration and gradually decreased to 0.3 ± 0.2 μg/ml at 24 hr following administration. The Cmax of ELF OBFX was 9.3 ± 0.4 μg/ml at 3.0 ± 2.0 hr post administration and gradually decreased to 1.2 ± 0.1 μg/ml at 24 hr following administration. The Cmax of alveolar cells OBFX was 9.3 ± 2.9 μg/ml at 4.0 hr post administration and gradually decreased to 1.1 ± 0.2 μg/ml at 24 hr following administration. The half-life of OBFX in plasma, ELF, and alveolar cells were 6.9 ± 2.2, 7.0 ± 0.6, and 7.8 ± 1.6 hr, respectively. The Cmax and the area under the concentration-time curve for 0–24 hr with OBFX were significantly higher in ELF and alveolar cells than in plasma (P<0.05). These results suggest that OBFX is distributed and retained at high concentrations in ELF and alveolar cells at 24 hr following administration. Hence, a single intramuscular dose of OBFX (5.0 mg/kg) may be an effective therapeutic agent against pneumonia. 相似文献
74.
为研究三苯双脒在绵羊体内动态变化的规律,采用方法如下:绵羊1次口服给药60、120、180 mg/kg体重3个剂量组,依据消除速率常数、吸收率常数、达峰时、血药浓度-时间曲线等主要药动学参数,经上海宏能软件有限公司开发的临床药物代谢动力学软件进行数据分析,符合血管外给药一级吸收一室模型,主要药动学参数为:吸收率常数Ka=0.15129h,t1/2Ka=4.74h,消除速率常数Ke=0.082 121h,t1/2Ke=8.46h,t1/2=19.03 h,达峰时tmax=8.0 h,Cmax=6257μg/L,血药浓度-时间曲线下面积AUC=300 51μg/L.h。三苯双脒肠溶片在羊体内吸收快、半衰期长等特点。说明三苯双脒肠溶片在药效试验剂量范围内比较安全。 相似文献
75.
Goodwin WA Keates HL Pasloske K Pearson M Sauer B Ranasinghe MG 《Veterinary anaesthesia and analgesia》2011,38(5):431-438
ObjectiveTo determine the pharmacokinetics and pharmacodynamics of the neurosteroidal anaesthetic, alfaxalone, in horses after a single intravenous (IV) injection of alfaxalone, following premedication with acepromazine, xylazine and guaiphenesin.Study designProspective experimental study.AnimalsTen (five male and five female), adult, healthy, Standardbred horses.MethodsHorses were premedicated with acepromazine (0.03 mg kg?1 IV). Twenty minutes later they received xylazine (1 mg kg?1 IV), then after 5 minutes, guaiphenesin (35 mg kg?1 IV) followed immediately by IV induction of anaesthesia with alfaxalone (1 mg kg?1). Cardiorespiratory variables (pulse rate, respiratory rate, pulse oximetry) and clinical signs of anaesthetic depth were evaluated throughout anaesthesia. Venous blood samples were collected at strategic time points and plasma concentrations of alfaxalone were assayed using liquid chromatography-mass spectrometry (LC/MS) and analysed by noncompartmental pharmacokinetic analysis. The quality of anaesthetic induction and recovery was scored on a scale of 1–5 (1 very poor, 5 excellent).ResultsThe median (range) induction and recovery scores were 4 (3–5) (good: horse slowly and moderately gently attained recumbency with minimal or no rigidity or paddling) and 4 (1–5) (good: horse stood on first attempt with some knuckling and ataxia) respectively. The monitored cardiopulmonary variables were within the range expected for clinical equine anaesthesia. The mean ± SD durations of anaesthesia from induction to sternal recumbency and from induction to standing were 42.7 ± 8.4 and 47 ± 9.6 minutes, respectively. The mean ± SD plasma elimination half life (t1/2), plasma clearance (Clp) and volume of distribution (Vd) for alfaxalone were 33.4 minutes, 37.1 ± 11.1 mL minute?1 kg?1 and 1.6 ± 0.4 L kg?1, respectively.Conclusions and clinical relevanceAlfaxalone, in a 2-hydroxypropyl-beta-cyclodextrin formulation, provides anaesthesia with a short duration of recumbency that is characterised by a smooth induction and satisfactory recovery in the horse. As in other species, alfaxalone is rapidly cleared from the plasma in the horse. 相似文献
76.
Benjamin Kimble Larry Vogelnest Soraya Gharibi Aaron M. Izes Merran Govendir 《Journal of veterinary pharmacology and therapeutics》2020,43(2):115-122
Amoxicillin was administered as a single subcutaneous injection at 12.5 mg/kg to four koalas and changes in amoxicillin plasma concentrations over 24 hr were quantified. Amoxicillin had a relatively low average ± SD maximum plasma concentration (Cmax) of 1.72 ± 0.47 µg/ml; at an average ± SD time to reach Cmax (Tmax) of 2.25 ± 1.26 hr, and an elimination half-life of 4.38 ± 2.40 hr. The pharmacokinetic profile indicated relatively poor subcutaneous absorption. A metabolite was also identified, likely associated with glucuronic acid conjugation. Bacterial growth inhibition assays demonstrated that all plasma samples other than t = 0 hr, inhibited the growth of Escherichia coli ATCC 25922 and Staphylococcus aureus ATCC 29213 to some extent. Calculated pharmacokinetic indices were used to predict whether this dose could attain a plasma concentration to inhibit some susceptible Gram-negative and Gram-positive pathogens. It was predicted that a twice daily dose of 12.5 mg/kg would be efficacious to inhibit susceptible bacteria with an amoxicillin minimum inhibitory concentration (MIC) ≤ 0.75 µg/ml such as susceptible Bordetella bronchiseptica, E. coli, Staphylococcus spp. and Streptococcus spp. pathogens. 相似文献
77.
Zhoumeng Lin Miao Li Yu-Shin Wang Lisa A. Tell Ronald E. Baynes Jennifer L. Davis Thomas W. Vickroy Jim E. Riviere 《Journal of veterinary pharmacology and therapeutics》2020,43(5):385-420
Physiologically based pharmacokinetic (PBPK) models for chemicals in food animals are a useful tool in estimating chemical tissue residues and withdrawal intervals. Physiological parameters such as organ weights and blood flows are an important component of a PBPK model. The objective of this study was to compile PBPK-related physiological parameter data in food animals, including cattle and swine. Comprehensive literature searches were performed in PubMed, Google Scholar, ScienceDirect, and ProQuest. Relevant literature was reviewed and tables of relevant parameters such as relative organ weights (% of body weight) and relative blood flows (% of cardiac output) were compiled for different production classes of cattle and swine. The mean and standard deviation of each parameter were calculated to characterize their variability and uncertainty and to allow investigators to conduct population PBPK analysis via Monte Carlo simulations. Regression equations using weight or age were created for parameters having sufficient data. These compiled data provide a comprehensive physiological parameter database for developing PBPK models of chemicals in cattle and swine to support animal-derived food safety assessment. This work also provides a basis to compile data in other food animal species, including goats, sheep, chickens, and turkeys. 相似文献
78.
79.
Miao Li Christine Mainquist‐Whigham Locke A. Karriker Larry W. Wulf Dongping Zeng Ronette Gehring Jim E. Riviere Johann F. Coetzee Zhoumeng Lin 《Journal of veterinary pharmacology and therapeutics》2019,42(4):461-475
Penicillin G is widely used in food‐producing animals at extralabel doses and is one of the most frequently identified violative drug residues in animal‐derived food products. In this study, the plasma pharmacokinetics and tissue residue depletion of penicillin G in heavy sows after repeated intramuscular administrations at label (6.5 mg/kg) and 5 × label (32.5 mg/kg) doses were determined. Plasma, urine, and environmental samples were tested as potential antemortem markers for penicillin G residues. The collected new data and other available data from the literature were used to develop a population physiologically based pharmacokinetic (PBPK) model for penicillin G in heavy sows. The results showed that antemortem testing of urine provided potential correlation with tissue residue levels. Based on the United States Department of Agriculture Food Safety and Inspection Service action limit of 25 ng/g, the model estimated a withdrawal interval of 38 days for penicillin G in heavy sows after 3 repeated intramuscular injections at 5 × label dose. This study improves our understanding of penicillin G pharmacokinetics and tissue residue depletion in heavy sows and provides a tool to predict proper withdrawal intervals after extralabel use of penicillin G in heavy sows, thereby helping safety assessment of sow‐derived meat products. 相似文献
80.
Zeynep Ozdemir Hatice Eser Faki Kamil Uney Bunyamin Tras 《Journal of veterinary pharmacology and therapeutics》2019,42(5):497-504
The purpose of this study was to determine the pharmacokinetic interaction between ivermectin (0.4 mg/kg) and praziquantel (10 mg/kg) administered either alone or co‐administered to dogs after oral treatment. Twelve healthy cross‐bred dogs (weighing 18–21 kg, aged 1–3 years) were allocated randomly into two groups of six dogs (four females, two males) each. In first group, the tablet forms of praziquantel and ivermectin were administered using a crossover design with a 15‐day washout period, respectively. Second group received tablet form of ivermectin plus praziquantel. The plasma concentrations of ivermectin and praziquantel were determined by high‐performance liquid chromatography using a fluorescence and ultraviolet detector, respectively. The pharmacokinetic parameters of ivermectin following oral alone‐administration were as follows: elimination half‐life (t1/2λz) 110 ± 11.06 hr, area under the plasma concentration–time curve (AUC0–∞) 7,805 ± 1,768 hr.ng/ml, maximum concentration (Cmax) 137 ± 48.09 ng/ml, and time to reach Cmax (Tmax) 14.0 ± 4.90 hr. The pharmacokinetic parameters of praziquantel following oral alone‐administration were as follows: t1/2λz 7.39 ± 3.86 hr, AUC0–∞ 4,301 ± 1,253 hr.ng/ml, Cmax 897 ± 245 ng/ml, and Tmax 5.33 ± 0.82 hr. The pharmacokinetics of ivermectin and praziquantel were not changed, except Tmax of praziquantel in the combined group. In conclusion, the combined formulation of ivermectin and praziquantel can be preferred in the treatment and prevention of diseases caused by susceptible parasites in dogs because no pharmacokinetic interaction was determined between them. 相似文献