硫酸锰在肉鸡体内药代动力学研究

实验研究了30日龄肉鸡按55.38mg/Kg.体质量剂量灌服10%硫酸锰溶液后不同时间采血,应用石墨炉原子吸收分光光度法测定血药浓度,经微机处理得出血药浓度及药动学参数,血药浓度-时间曲线符合一级吸收一室开放模型,最佳药时方程:C=80.8013(e-0.0709t-e-0.4402t)。主要药动学参数:t1/2Ka为1.5747hrs,t1/2Ke为9.7698hrs,tp为5.6617hrs,Cmax为48.3581ug/L,AUC为967.9305(μg/L).h。根据单剂量给药参数,计算出多剂量给药参数。τ定为12h,(C∝)max为95.997μg/L,c为80.6609μg/L,(C∝)min为4.0668μg/L,D*为3.2794mg/Kg.BW,D0为1.8789mg/Kg.BW,R为1.7454。     

Pharmacokinetics and distribution of minocycline in mature horses after oral administration of multiple doses and comparison with minimum inhibitory concentrations

Reasons for performing study: Minocycline holds great potential for use in horses not only for its antimicrobial effects but also for its anti‐inflammatory and neuroprotective properties. However, there are no pharmacokinetic or safety data available regarding the use of oral minocycline in horses. Objectives: To determine pharmacokinetics, safety and penetration into plasma, synovial fluid, aqueous humour (AH) and cerebral spinal fluid (CSF) of minocycline after oral administration of multiple doses in horses and to determine the minimum inhibitory concentrations (MIC) of minocycline for equine pathogenic bacteria. Methods: Six horses received minocycline (4 mg/kg bwt q. 12 h for 5 doses). Thirty‐three blood and 9 synovial fluid samples were collected over 96 h. Aqueous humour and CSF samples were collected 1 h after the final dose. Minocycline concentrations were measured using high pressure liquid chromatography. The MIC values of minocycline for equine bacterial isolates were determined. Results: At steady state, the mean ± s.d. peak concentration of minocycline in the plasma was 0.67 ± 0.26 µg/ml and the mean half‐life was 11.48 ± 3.23 h. The highest trough synovial fluid minocycline concentration was 0.33 ± 0.12 µg/ml. The AH concentration of minocycline was 0.09 ± 0.03 µg/ml in normal eyes and 0.11 ± 0.04 µg/ml in blood aqueous barrier‐disrupted eyes. The mean CSF concentration of minocycline was 0.38 ± 0.09 µg/ml. The MIC values were determined for 301 isolates. Minocycline concentrations were above the MIC₅₀ and MIC₉₀ for many gram‐positive equine pathogens. Potential relevance: This study supports the use of orally administered minocycline at a dose of 4 mg/kg bwt every 12 h for the treatment of nonocular infections caused by susceptible (MIC≤0.25 µg/ml) organisms in horses. Further studies are required to determine the dose that would be effective for the treatment of ocular infections.     

Population Pharmacokinetics of Tobramycin in Horses

Population pharmacokinetics of tobramycin was investigated in 28 healthy horses, with an aim to assess interindividual variability in the disposition of the antibiotic. Additionally, a covariate model for improved prediction of the concentrations in a particular animal was developed. A two-compartmental model best described the data. The final population covariate regression model was based on relationships between body weight and central and peripheral volumes of distribution, and between creatinine clearance and systemic tobramycin clearance. The value of population systemic tobramycin clearance and its interindividual variation (CV) were 0.087 L.hr⁻¹.kg⁻¹ and 6.0%, respectively. The respective values for central and peripheral volumes of distribution were 0.652 L.kg⁻¹ with CV of 17.7% and 1.56 L.kg⁻¹ with CV of 4.5%. In horses with decreased glomerular filtration rate, lower tobramycin clearance is predicted with the population model that requires administration of lower dose than that accepted for treatment of horses with normal kidney function. Population pharmacokinetic analysis allows study of basic disposition of tobramycin in horses with sparse data. The prediction power of the regression model was improved by inclusion of covariables such as body weight and creatinine clearance. This model can be used in direct patient care for the construction of dosing strategy in individual clinical cases.     

千里光提取物冻干粉药代动力学研究-抗炎药理效应法

为了探索千里光提取物冻干粉(SsE)的药物代谢动力学特征,首次采用耳肿胀度抑制率药理效应法测定SsE药动学参数。结果发现,在一定剂量范围内给小鼠腹腔注射SsE,能较迅速地产生药理效应,使耳肿胀度抑制率显著提高;SsE最低有效量为57.40 mg/kg,在小鼠体内代谢符合一级反应一室模型,模型表达式为:C=1 436.227 e^(-0.133 4 t)-1436.227 e^(-0.237 t),表观药动学参数为:一级消除速率常数Ke=0.133 4 h-1,消除半衰期t1/2Ke=5.194 9 h,一级吸收速率常数Ka=0.237 h-1,吸收半衰期t1/2Ka=2.924 1 h,血药峰浓度Cmax=1 436.227 mg/kg,达峰时间tmax=5.547 4 h,清除率Cl=0.055 3mg/kg.h,药-时曲线下面积AUC=16 826.35 mg/kg.h,表观分布容积V=0.414 2 mg/kg,滞后期t0=0.010 4 h。表明SsE具有良好的抗炎作用,在小鼠体内起效快,消除慢,生物利用度高,在机体内分布有限,较集中于血浆,组织摄入少。     

Aspects of the Pharmacokinetics of Albendazole Sulphoxide in Sheep

The plasma disposition kinetics of albendazole sulphoxide (ABZSO), ((+)ABZSO and (–)ABZSO) and its sulphone metabolite (ABZSO₂) were investigated in adult sheep. Six Corriedale sheep received albendazole sulphoxide by intravenous injection at 5 mg/kg live weight. Jugular blood samples were taken serially for 72 h and the plasma was analysed by high-performance liquid chromatography (HPLC) for albendazole (ABZ), ABZ sulphoxide (ABZSO) and albendazole sulphone (ABZSO₂). Albendazole was not detected in the plasma at any time after the treatment, ABZSO and ABZSO₂ being the main metabolites detected between 10 min and 48 h after treatment. A biexponential plasma concentration versus time curve was observed for both ABZSO and ABZSO₂ following the intravenous treatment. The plasma AUC values for ABZSO and ABZSO₂ were 52.0 and 10.8 (g.h)/ml, respectively. The ABZSO₂ metabolite was measurable in plasma between 10 min and 48 h after administration of ABZSO, reaching a peak concentration of 0.38 g/ml at 7.7 h after treatment. Using a chiral phase-based HPLC method, a biexponential plasma concentration versus time curve was observed for both ABZSO enantiomers. The total body clearance was higher for the (–) than for the (+) enantiomer, the values being 270.6 and 147.75 (ml/h)/kg, respectively. The elimination half-life of the (–) enantiomer was shorter than that of the (+) enantiomer, the values being 4.31 and 8.33 h, respectively. The enantiomeric ratio (+)ABZSO/(–)ABZSO at t ₀ was close to unity. However, the ratio in the plasma increased with time.     

Endometrial Tissue Concentrations of Enrofloxacin after Intrauterine Administration to Mares

Endometritis in mares is a common cause of infertility. Conventional treatments of the disease have mostly been unsuccessful, so new therapeutic alternatives need to be investigated. This study evaluated the uterine disposition and plasma pharmacokinetic behaviour of a commercial formulation of enrofloxacin (EFX) given by the intrauterine (i.u.) route (2.5 mg/kg) in healthy mares. In order to evaluate the uterine inflammatory response, an initial histopathological study assessing polymorphonuclear cell infiltration was carried out in 20 mares over a 14-day period after treatment. In a second study, 6 healthy adult mares were used for the pharmacokinetic study. Samples of uterine tissue and plasma were collected from 0 to 24 h after the i.u. treatment with 5% EFX solution. Samples were analysed by conventional microbiological assay using an EFX-sensitive strain of Escherichia coli (ATCC 25922). There was a moderate but statistically nonsignificant inflammatory response following i.u. administration of either the formulation or the vehicle alone. Pharmacokinetic analysis of the uterine concentrations of EFX showed a slow and sustained depletion, with EFX remaining at concentrations above the MIC for 24 h after treatment. The area under the concentration–time curve obtained for the uterus suggested that EFX and its metabolites are specifically retained in the uterus, which is the target tissue for bacterial colonization. Neither study provided any evidence of EFX toxicity. In conclusion, these results are encouraging and suggest that EFX may be a useful local treatment in mares with bacterial endometritis.     

Dermal pharmacokinetics of the insecticide furathiocarb in rats

The pharmacokinetics of furathiocarb were studied in vivo in male Sprague-Dawley rats following dermal treatment. HPLC and post-column derivatization were used for the analysis of furathiocarb and its metabolites (carbofuran, 3-hydroxycarbofuran and 3-ketocarbofuran). Carbofuran and 3-hydroxycarbofuran were detected in plasma and urine rather than furathiocarb. 3-Ketocarbofuran, another potential metabolite, was not observed in any sample. The concentration of carbofuran was higher than that of 3-hydroxycarbofuran in plasma, but the reverse was the case in urine. The corresponding area under the plasma concentration-time curve, Tmax, and Cmax values of carbofuran and 3-hydroxycarbofuran for 1500 mg kg-1 doses were 2.4-8.0 mg equiv hml-1, 12 h and 0.1-0.4 mg equiv ml-1, respectively. T1/2 was calculated only for 3-hydroxycarbofuran (28 h). Two metabolites were excreted in a dose-dependent manner without saturation.     

The Pharmacokinetics of a Long-acting Oxytetracycline Formulation in Healthy Dogs and in Dogs Infected with Ehrlichia canis

The pharmacokinetic properties of oxytetracycline were studied following a single injection of a long-acting formulation (20 mg/kg body weight) into the semimembranosus muscle of healthy dogs and of dogs that had been experimentally infected with Ehrlichia canis. The disposition curves of the long-acting oxytetracycline formulation before and after infection were best described by a bi-exponential decline after a first-order absorption. The mean maximum serum concentration (C _max) following infection was significantly lower and the time taken to attain this concentration (t _max) was significantly shorter than that in the healthy dogs. The mean apparent elimination half-life (t _1/2) was significantly increased following infection. The corresponding rate constant () was significantly decreased. The absorption half-life (t _1/2ab) was significantly decreased after infection. The volume of distribution at steady state (V _dss) increased significantly following infection. It was concluded that the pharmacokinetic behaviour of a long-acting oxytetracycline in dogs after intramuscular administration is characterized by a two-compartment model with a slow elimination phase. This could be due to flip-flop kinetics. The febrile reaction in experimental E. canis infection affected some pharmacokinetic parameters of oxytetracycline.     

Pharmacokinetics of Enrofloxacin and Its Metabolite Ciprofloxacin after Intramuscular Administration of Enrofloxacin in Goats

The pharmacokinetics of enrofloxacin and its active metabolite ciprofloxacin were investigated in goats after a single intramuscular administration of enrofloxacin at 2.5 mg/kg body weight. The plasma concentrations of enrofloxacin and ciprofloxacin were determined simultaneously by a HPLC method. The peak concentrations (C _max) of enrofloxacin (1.13 g/ml) and ciprofloxacin (0.24 g/ml) were observed at 0.8 and 1.2 h, respectively. The elimination half-life (t _1/2), volume of distribution (V _d(area)), total body clearance (Cl_B) and mean residence time (MRT) of enrofloxacin were 0.74 h, 1.42 L/kg, 1329 ml/h per kg and 1.54 h, respectively. The t _1/2, area under the plasma concentration–time curve (AUC) and the MRT of ciprofloxacin were 1.38 h, 0.74 g h/ml and 2.73 h, respectively. The metabolic conversion of enrofloxacin to ciprofloxacin was appreciable (36%) and the sum of the plasma concentrations of enrofloxacin and ciprofloxacin was maintained at or above 0.1 g/ml for up to 4 h. Enrofloxacin appears to be useful for the treatment of goat diseases associated with pathogens sensitive to this drug.     

穿心莲兽医药理学研究进展

文章综述了近年来国内对穿心莲的化学成分,色谱指纹图谱,对动物体生理功能的影响,药代动力学以及毒副作用的兽医药理学研究新进展.