The influence of growth and E. coli endotoxaemia on amoxicillin pharmacokinetics in turkeys

1. This experiment aimed to determine if the pharmacokinetics of amoxicillin (AMO) was affected by rapid growth or intravenous (i.v.) injection of Escherichia coli lipopolysaccharide (LPS).

2. Turkeys of 2.0, 5.5 and 12.0 kg were administered i.v. or orally with AMO sodium at the dose of 15 mg/kg. Another group (5.7 kg) was treated with LPS prior to i.v. AMO administration. Plasma drug concentrations were determined using high-performance liquid chromatography and pharmacokinetic parameters were calculated using a non-compartmental model. To assess the haemodynamic effects of endotoxaemia, turkeys were subjected to echocardiography.

3. During growth from 2.0 to 5.5 kg, the area under the drug concentration-time curve after i.v. AMO administration increased from 9.37 ± 2.43 to 21.29 ± 5.49 mg×h/ml. Total body clearance decreased from 1.72 ± 0.55 to 0.75 ± 0.12 l/h/kg. Growth to 12.0 kg did not further affect these parameters. Mean residence time and elimination half-life gradually increased. Pharmacokinetics of orally administered drug followed a similar pattern. LPS injection affected stroke volume, heart rate and resistance index. However, it did not affect the pharmacokinetic profile of AMO in survivors.

4. It is concluded that rapid growth in turkeys affects AMO pharmacokinetics. Endotoxaemia, on the other hand, does not affect AMO elimination if compensatory mechanisms develop.     

Comparative pharmacokinetics of acetylsalicylic acid and sodium salicylate in chickens and turkeys

1. Pharmacokinetics of acetylsalicylic acid (ASA) and sodium salicylate (SS) were assessed following single intravenous (i.v.) and oral administration at doses of 50 mg/kg body weight to chickens and turkeys. Plasma drug concentrations were determined using high-performance liquid chromatography with ultraviolet detection and pharmacokinetic variables were calculated using a non-compartmental model.

2. The mean residence time (MRT) of salicylate (SA) after i.v. administration of SS was 6.08 ± 0.59 and 3.32 ± 0.27 h and after oral administration was 6.95 ± 0.72 and 4.55 ± 0.71 h in chickens and turkeys, respectively. The elimination half-life (T _{1/2 e}) was shorter in turkeys compared with chickens. The value of body clearance (Cl_B) was higher in turkeys than in chickens, but the apparent volume of distribution (V _ss) was similarly low in both species. The bioavailability of SS was complete and the maximal plasma concentration of SA (C _max) after oral administration was 96.93 ± 8.06 and 91.76 ± 9.64 µg/ml, respectively, in chickens and turkeys.

3. The MRT of ASA after iv administration was 0.24 ± 0.08 and 0.24 ± 0.02 h and after oral administration was 0.78 ± 0.25 and 0.59 ± 0.13 h, respectively, in chickens and turkeys. In both species, T _{1/2 e} was very short, Cl_B and V _ss were similar and markedly higher than those of salicylate. The bioavailability of unchanged ASA was low and C _max after oral administration was 6.9 ± 3.6 µg/ml in chickens and 8.6 ± 1.3 µg/ml in turkeys.     

头孢噻呋钠在猪体内的药代动力学和生物利用度研究

用微生物杯蝶法测定血清药物浓度,6头实验猪按5 mg/kg单剂量静注、肌注头孢噻呋钠(Ceftiofur Sodium),对其药代动力学和生物利用度进行了研究.试验菌为蜡样芽孢杆菌1.1687,结果平均回收率为96.52%,血清最低检测浓度为0.15 μg/ml,日内日间变异系数为2.5%～4.9%,血清浓度在0.3～0.8 μg/ml范围内呈良好线性关系(r=0.9884).药时数据经Mcpkp药代动力学计算机程序处理,猪静注、肌注头孢噻呋钠体内药物运转都符合二室开放模型,其中静注的药代动力学参数为T1/2α=2.22 h,T1/2β=14.64 h, K12=0.09/h, K21=0.078/h, Kel=0.20/h, V1=0.34 l/kg, VB =1.38 l/kg, CLB=0.07 l/kg/h,AUC=76.56 mg/l*h; 肌注药代动力学参数为Tmax=0.69 h,Cmax=12.09 μg/ml,T1/2ka=0.19 h,T1/2β=15.18 h,Kel=0.23/h,K12=0.14/h,K21=0.08/h;生物利用度为AUCi.m/AUCi.v=87.97%.     

Relevance of age at slaughter on meat quality of turkeys stunned with CO2

1. The objective of this work was to determine the effect of slaughter age and stunning method on the quality of turkey meat from poultry processing plants.

2. One hundred B.U.T. Premium turkeys were divided into 4 groups of 25 animals according to slaughter age (15 or 17 weeks) and CO₂ stunning procedure (G1 stepwise: step1: 30% CO₂, 15 s; step 2: 55% CO₂, 40 s; step 3: 70% CO₂, 45 s; G2: progressive increase of the CO₂ concentration at a rate of 0.8% per s for 100 s). The quality of the breast meat was determined in fillets taken at different post-mortem times.

3. There were differences between the stunning groups for several variables (pH: 6.01 ± 0.01 and 5.95 ± 0.02; a*: ?1.84 ± 0.05 and ?2.21 ± 0.04; b*: 4.99 ± 0.15 and 4.68 ± 0.16; drip loss: 0.85 ± 0.02 and 0.71 ± 0.02 for G1 and G2, respectively), while no significant differences were found for L*, cooking loss and texture analysed with a Warner Bratzler Shear Force cell (WBSF).

4. Slaughter age had a significant effect on all the parameters studied (pH: 6.01 ± 0.01 and 5.95 ± 0.01; a*: ?2.21 ± 0.05 and ?1.88 ± 0.05, b*: 5.50 ± 0.17 and 4.42 ± 0.15; drip loss: 0.71 ± 0.02 and 0.86 ± 0.02, cooking loss: 12.56 ± 0.22 and 14.69 ± 0.16 for turkeys slaughtered at 15 and 17 w, respectively) except on L* and WBSF.

5. The ageing of the meat affected pH, colour values, drip loss and WBSF, with differing degrees of evolution: mean values of L* (39.36 ± 0.35. 45.77 ± 0.20 and 46.30 ± 0.24, for 20 min, 24 h and 7 d post mortem, respectively) and drip loss (0.75 ± 0.03 and 0.84 ± 0.02 for 24 h and 7 d post mortem, respectively) increased, those of a* (?1.77 ± 0.08, ?1.94 ± 0.07 and ?2.22 ± 0.05 for 20 min, 24 h and 7 d post mortem, respectively) and WBSF decreased (3.73 ± 0.06 and 2.63 ± 0.04 for 24 h and 7 d post mortem, respectively), those of pH decreased in the first 24 h and remained stable for the next 6 d (6.19 ± 0.02, 5.87 ± 0.01 and 5.88 ± 0.01), and those of b* increased in the first 24 h post-mortem and remained stable for the next 6 d (3.26 ± 0.31, 5.86 ± 0.16 and 5.47 ± 0.08).

6. The results revealed no critical differences between stunning methods, and suggest that animals slaughtered at 15 weeks present higher quality meat than those slaughtered at 17 weeks.     

The influence of age on the pharmacokinetics of aditoprim in pigs after intravenous and oral administration

Some pharmacokinetic parameters of aditoprim were determined in 3- and 6-month-old pigs. After intravenous administration of 5 mg/kg body weight, the mean total body clearance of the older pigs was smaller than that of the younger pigs. This difference was not reflected in the elimination half-life. After oral administration of 5 mg/kg body weight, the mean absorption rate constant was smaller and the mean absorption half-life was longer in the older pigs. The age-related changes in the pharmacokinetics of aditoprim were not sufficiently pronounced to suggest the necessity of modifying the oral dosage regimen in pigs of this age range. The favourable pharmacokinetics of aditoprim in pigs (large apparent volume of distribution, long elimination half-life and high bioavailability) may permit introduction of this drug into swine practice, after safety and residue depletion studies.     

Accidental finding of Hashimoto‐like thyroiditis in male B.U.T. 6 turkeys at slaughter

In the context of a study on the tolerance of rapeseed meal in B.U.T. 6 turkeys, thyroid glands were histologically and immunohistochemically examined because of potential thyreostatic effects. In all groups including the controls with no rapeseed meal in their food, there was a high incidence of lymphocytic infiltration and thyroiditis (14% of thyroids with moderate to severe lymphocytic thyroiditis). Thirty per cent of mononuclear inflammatory cells were immunohistochemically identified as T cells. There were occasional accumulations of PAX‐5 labelled cells, indicating germinal centre development. These lesions resemble Hashimoto's disease in humans. The effect on thyroid function is unknown. Mild hypothyreosis might enhance productivity but also explain dispositions towards diseases seen in context with thyroid dysfunction such as skin diseases (foot pad disease?) and cardiovascular problems. Further studies on thyroid function in these turkeys are needed.     

Routes of transmission of Salmonella and Campylobacter in breeder turkeys

Salmonella and Campylobacter are frequent colonizers of the intestinal tracts of poultry and have often been associated with human foodborne illness. The entry, transmission, and prevalence of both pathogens have been extensively studied in chickens but little information is available for turkeys. This project monitored turkey breeder hens and toms from d of hatch to 65 wk of age with the objective of determining routes of transmission for Salmonella and Campylobacter throughout the turkey production cycle. Breeder poults were separated by sex and then into 2 groups (control and inoculated) for each sex. The inoculated group was orally gavaged with marker strains of both Salmonella and Campylobacter. The inoculated groups (toms and hens) were placed on the opposite side of a growout house from the uninoculated groups. Fecal samples, intestinal samples and organs, feed, drinkers, and potential vectors such as insects and mice, were analyzed at different times until 65 wk. Monitoring showed that Campylobacter spread rapidly and cross-contaminated turkeys throughout the growout house. For both Salmonella and Campylobacter, naturally occurring strains that were first isolated in control groups at wk 3 and 4, respectively, outcompeted marker strains several wk post inoculation and persisted in the flock. The most common naturally occurring strains were C. jejuni (tetracycline resistant), C. coli (kanamycin resistant), and S. Agona. Campylobacter and Salmonella also were isolated from flies and from a mouse, confirming the importance of proper pest control and biosecurity to reduce the spread of the bacteria.     

水杨酸钠对兔体内青霉素G钠药动学及组织分布的影响

给兔体肌注青霉素Ｇ钠，同时静注水杨酸钠，给药后不同时间采样，用微生物管碟法测定血药浓度及组织中的浓度，观察了水杨酸钠对兔体内青霉素Ｇ钠药动学及组织分布的影响。实验兔的药时数据符合有吸收因素二室开放模型。与对照组比较，实验组的动力学参数β、Ｋ２１、Ｋｅｌ的值显著减小，而参数Ｋ１２、ｔ１／２β、ＡＵＣ、ＴＣＰ的值显著增加。对照组与实验组的青霉素Ｇ钠在血液与肝、肾、肺或肌肉间的分布没有显著差异。     

1日龄火鸡新城疫免疫后局部体液免疫球蛋白含量的动态变化

本实验应用Lasota苗及其灭活苗联合免疫接种1日龄火鸡,60日龄攻毒。分别在免疫后第7、14、21、35和60日检泪液、气管液、胆汁和肠道冲洗液中IgG、IgM、IgA含量及泪液HI抗体滴度的动态变化。结果表明免疫火鸡上述各项指标明显高于对照,联合免疫组高于Lasota单独免疫组,说明火鸡早期免疫可明显提高呼吸道和消化道相关局部体液的抗体水平和抗感染能力,其中联合免疫优于单独弱毒苗免疫。     

健康仔猪口服亚硒酸钠后血液中药代动力学的研究

本实验按 0 .6 mg/ kg BW单剂量对健康仔猪口服亚硒酸钠溶液后 ,首次系统地研究了其在血液中药物代谢动力学。实验结果表明 :血液动力学特征符合一级吸收二室开放模型 ,其理论方程为 :C=0 .0 82 0 e- 0 .0 4 2 1 t 0 .10 5 0 e- 0 .0 0 1 4t- 0 .1870 e- 2 .2 541 t。主要动力学参数为 :吸收半衰期 (t1 / 2 Ka)为 0 .30 75 h;达峰时间 (tmax)为 2 .15 17h;消除半衰期 (t1 / 2β)为 5 10 .2 70 6 h;曲线下面积 (AU C)为 75 .14 6 0 mg/ L· h;表观分布容积 (Vd)为 5 .5 74 2 L/ kg。根据单剂量药动学参数 ,计算多剂量给药参数 ,为临床治疗制订给药方案。先导剂量 (D* )为 1.2 2 6 2 mg/ kg BW,维持剂量(D0 )为 0 .6 m g/ kg BW,给药间隔 (τ)为 4 80 h,平均稳态血药浓度 (с)为 0 .15 6 6 μg/ m l     

Metronidazole pharmacokinetics during rapid growth in turkeys – relation to changes in haemodynamics and drug metabolism

Whereas interspecies variation in pharmacokinetics is a commonly investigated issue, variations in drug kinetics within a species are less documented. The aim of the study was to assess the influence of age‐related changes in haemodynamics on the pharmacokinetics of metronidazole (MTZ) and its hydroxy metabolite (MTZ‐OH) in turkeys. MTZ was administered intravenously and orally at a dose of 25 mg/kg. Plasma drug and metabolite concentrations were assessed by high‐performance liquid chromatography, and pharmacokinetic parameters were calculated by noncompartmental analysis. Haemodynamic parameters (heart rate, stroke volume, cardiac output) were assessed by echocardiography and extraction ratio for MTZ was calculated based on total body clearance (Cl_B). Between the 5th and 15th week of age, Cl_B of MTZ decreased from 3.6 to 1.2 mL/min/kg causing a twofold increase in the mean residence time (MRT) and elimination half‐life (T_1/2el). The MTZ‐OH production decreased threefold and its MRT and T_1/2el increased. Although heart rate significantly decreased with age, cardiac output increased. Extraction ratio was low in all age groups. It is concluded that significant age‐dependent decrease in Cl_B of MTZ in turkeys resulted from decreased perfusion of the clearing organs and their reduced metabolic capacity. This phenomenon is probably species specific and may apply to other therapeutic agents.     

The pharmacokinetics of salicylate in dairy cattle are not altered by simultaneous intravenous ceftiofur sodium and DL-lysine-acetyl salicylate (Aspirin)

This study evaluated potential alterations to the pharmacokinetics of salicylate by concurrently administered ceftiofur sodium. The trial design was a crossover using 10 non-lactating, non-pregnant dairy cows. In the first period each cow received intravenously (IV) 26 mg/kg of DL-lysine acetyl salicylate (aspirin) followed immediately by 2 mg/kg ceftiofur sodium. In the second period each cow received 26 mg/kg of aspirin IV. Plasma samples were harvested for determination of salicylate concentration by HPLC. The data best fitted a single compartment open model, using weighted non-linear regression. No alterations to the pharmacokinetic parameters of salicylate in cattle by concurrently administered ceftiofur sodium were detected ( P <0.05). Using 90% confidence intervals, and testing for changes of > 20%. control values, elimination half-life ( t ₁/₂), apparent volume of distribution ( V _d), area under the plasma concentration versus time curve ( AUC ) and mean residence time ( MRT ) were not altered. For control animals the elimination rate constant ( k _el) and total body clearance ( Cl ) were 1.35/pm0.43 h⁻¹ and 20.2/pm6.1 ml/h.kg respectively (mean/pmSD). Since ceftiofur sodium did not affect the pharmacokinetics of salicylate, dose regimens for aspirin in cattle need not be altered when ceftiofur sodium is administered concurrently.     

腐殖酸钠对紫花苜蓿生长及生物量的影响

采用盆栽试验,研究腐殖酸钠肥(NaHA)单施及其与磷肥(P)配施对紫花苜蓿(Medicago sativa)生长特性及生物量的影响。结果表明,Na HA单施及其与P配施对紫花苜蓿生产指标均有一定的促进作用,且NaHA与P配施的促进作用更明显。NaHA与P配施条件下,当P水平一定时,紫花苜蓿生长速度、株高、节间数、节间距及生物量随NaHA施用量的增加呈现先增后减的趋势;当P从P_1(642 kg·hm~(-2))水平增至P_2(1 286 kg·hm~(-2))水平时,NaHA-P_2施肥组合对紫花苜蓿各生产指标的促进作用不及NaHA-P1组合显著。通过灰色关联度分析对供试处理各性状指标进行综合评价,得出Na HA5-P_1处理的综合表现最好,而且其获得的总生物量也最高。因此,Na HA5-P_1是该试验最佳的施肥组合,即Na HA为2 118 kg·hm~(-2),P为642 kg·hm~(-2)。     

Pharmacokinetics of Enrofloxacin and Its Metabolite Ciprofloxacin in Male and Female Turkeys following Intravenous and Oral Administration

The pharmacokinetics of enrofloxacin (EFL) was investigated in turkeys (6 male and 6 female; 7-month-old at the start of the experiment), after intravenous and oral administration at a dose of 10 mg/kg body weight. The serum concentrations of EFL and its active metabolite ciprofloxacin (CFL) were determined by high-performance liquid chromatography. The serum concentrations vs time were analysed by a compartmental analysis. The mean values of EFL pharmacokinetic parameters showed differences only between values of V_d,ss (3.46±0.19 for the females and 4.53±0.11 L/kg for the males, p>0.05). The metabolite CFL was eliminated more slowly than its parent compound. There were no statistically significant differences between the values of the CFL pharmacokinetic parameters calculated for both sexes, excluding the higher values (p>0.05) of C_max in the females. The ratio AUC_CFL/AUC_EFL×100 was 4.4% in the male and 6.84% in the female birds. After oral administration of EFL the values of F(%) were 77.83 in the female and 79.61 in the male turkeys. Higher CFL serum concentrations were measured in females (p>0.05). The pharmacokinetics of enrofloxacin and its metabolite ciprofloxacin in turkeys can be characterized as similar to that in chickens and very similar between both sexes.     

Oral doxycycline pharmacokinetics: Lambs in comparison with sheep

The pharmacokinetics of doxycycline was investigated in lactating sheep and lambs after oral administration at a dose of 10 mg/kg. Concentrations in plasma and milk were assayed with HPLC-PDA analysis. Doxycycline penetrates into the milk, and levels (0.38 ± 0.21 μg/ml) were found 0.5 hr after the treatment. The results suggest that the lambs can be exposed to doxycycline by suckling milk from their treated mothers. Population pharmacokinetic analysis showed a positive relationship between age, which reflects the stage of development of rumen function, and clearance. Possible explanations for the observed differences include the undeveloped rumen in lambs, the differences in the feed and liver function as evidenced by the blood biochemical parameters aspartate aminotransferase (AST) and alanine aminotransferase (ALT), which were significantly lower in lambs (62.67 ± 27.83 U/L and 8.50 ± 6.80 U/L) than in sheep (114.33 ± 20.77 U/L and 18.00 ± 3.16 U/L).     

亚硒酸钠在低硒雏鸡体内药代动力学的研究

采用低硒日粮（０．０２１μｇ／ｇ）饲喂１日龄蛋用雏鸡至１２～１４日龄（血硒降至０．０２３２±０．０１１０μｇ／ｍｌ）,按单剂量０．５２６ｍｇ／ｋｇＢＷ口服亚硒酸钠后不同时间点采集血样,用荧光分光光度法测定血硒浓度。应用ＭＣＰＫＰ药动学程序自动拟合处理血硒浓度——时间数据并求出药动学参数。血硒浓度－时间曲线符合一室开放模型,最佳药时方程为：Ｃｉ＝０．０９５９０（ｅ－０．００６１９ｔ－ｅ－０．０９４１０ｔ）。主要药动学参数：ｔ１２Ｋａ为２．０３ｈ,ｔ１２Ｋ为１１２．０２ｈ,ｔｐ为１１．９８ｈ,Ｃｍａｘ为０．０８７３８μｇ／ｍｌ,ＡＵＣ为１５．２１１ｍｇ／ｌ·ｈ。根据单剂量药动学参数,计算出多剂量给药参数：τ为１２０ｈ,Ｃ为０．１２６７６μｇ／ｍｌ,Ｄ＊为０．７０８１ｍｇ／ｋｇＢＷ,Ｄ０为０．３７１２ｍｇ／ｋｇＢＷ,Ｒ为１．９０７６。     

头孢噻呋钠混悬注射液在鹅体内的药代动力学

健康四川白鹅20只,随机分为A、B两组,A组单剂量静注头孢噻呋钠无菌粉针,B组单剂量肌注头孢噻呋钠混悬注射液,均按2．2mg·kg-1。用高效液相色谱法测定血浆中的药物浓度,3p97药代动力学程序软件处理药时数据。结果显示,A组药-时数据符合二室开放模型（W-1／C^2）;主要药代动力学参数：t1／2。0．112h,tmB2．711h,CL0．234L·kg-1·h-1,V0．064L·kg,AUC9．400mg·h·L-1,B组药-时数据也符合二室开放模型（W-1／c2）;主要药代动力学参数：t1/2结果表明,头孢噻呋钠混悬注射液在鹅体内分布广泛,生物利用度高,且具有长效缓释作用.。     

亚硒酸钠在低硒雏鸡体内组织药动学的研究

低硒雏鸡按单剂量0．526mg／kgBW口服亚硒酸钠后在不同时间点采集肝、肾、胰、心、肺、脾、十二指肠和胸肌,用荧光分光光度法测定组织硒浓度。应用微机MCPKP药动学程序自动拟合组织硒浓度－时间数据并求药动学参数。结果显示,心、肺、十二指肠符合一定开放模型,肝、肾、脾、胰符合二室开放摸型,肌肉符合吸收滞后二室开放模型。吸收以肝、十二指肠为最快,肾、胰、心、肺、脾依次减慢,肌肉吸收最慢,并有一个滞后期。组织中硒的消除均较缓慢。