Kinetics and residues after intraperitoneal procaine penicillin G administration in lactating dairy cows

This paper describes the pharmacokinetic profile of procaine penicillin G after intraperitoneal (IP) administration in eight lactating dairy cows. Procaine pencillin G (PPG, 21 000 IU/kg) was deposited into the abdominal cavity of each cow following an incision in the right paralumbar fossa. Blood and milk samples were taken over the following 10 days, at which point the cows were euthanized. Plasma, milk, muscle, liver, and kidney penicillin concentrations were determined by HPLC, with a limit of quantification of 5 ng/mL for plasma and milk and 40 ng/g for tissue samples. A noncompartmental method was used to analyze plasma kinetics. The mean pharmacokinetic parameters (±SD) were: C _max, 5.5 ± 2.6 μg/mL; T _max, 0.75 ± 0.27 h; AUC _0-∞, 10.8 ± 4.9 μg·h/mL; MRT , 2.2 ± 0.9 h. All milk from treated cows contained detectable penicillin residues for a minimum of three milkings (31 h) and maximum of five milkings (52 h) after administration. Concentrations of penicillin in all muscle, liver, and kidney samples taken 10 days postadministration were below the limit of quantification. Necropsy examinations revealed foci of hemorrhage on the rumenal omentum of most cows but peritonitis was not observed. Systemic inflammation as determined by change in leukogram or plasma fibrinogen was noted in one cow. The results of this study demonstrate that IP PPG is absorbed and eliminated rapidly in lactating dairy cows.     

Effect of the injection site on the pharmacokinetics of procaine penicillin G in horses

The plasma penicillin concentrations were determined in 5 horses given an IV injection of sodium penicillin G; plasma penicillin concentrations were also determined in a crossover experiment, where animals were given procaine penicillin G subcutaneously at 1 site and IM at 4 sites. The mean penicillin plasma peak concentration and bioavailability were highest after the drug was injected in the neck and biceps musculature. Injections in the gluteal muscle and in the subcutaneous sites resulted in similar, but lower, more persistent penicillin plasma concentrations and a lower bioavailability than were obtained with injection in the neck and biceps musculature. The pharmacokinetic data obtained after penicillin was administered via the pectoral muscle route exhibited an intermediate position. Therapeutic implications of the routes of administration with respect to hemolytic streptococcal infections are discussed.     

Antibiotic residues in milk following bulbar subconjunctival injection of procaine penicillin G in dairy cows

OBJECTIVE: To determine whether, and at what time, penicillin enters milk at a concentration that is detectable following bulbar subconjunctival injection in lactating dairy cows. DESIGN: Randomized clinical trial. ANIMALS: 66 Holstein cows that were at least 2 weeks past calving and had not been treated with antibiotics in the preceding 30 days. PROCEDURE: Cows were randomly assigned to receive a treatment of 1 ml (300,000 units) procaine penicillin G by bulbar subconjunctival injection or remain untreated. Composite milk samples were collected immediately before treatment and 4, 10, 16, 22, 28, and 40 hours after treatment. Milk samples were tested by use of a commercial test for beta-lactam antibiotics. RESULTS: Among penicillin-treated cows, the first positive test results were observed 4 hours after treatment, and the last positive result was observed 22 hours after treatment. The percentages of positive test results before treatment and at 4, 10, 16, 22, 28, and 40 hours after treatment were 0, 9, 87, 42, 8, 0, and 0%, respectively. None of the untreated cows had positive test results for beta-lactam antibiotics at any sampling time. CONCLUSIONS AND CLINICAL RELEVANCE: Penicillin was detected in milk for up to 22 hours after a single subconjunctival injection of procaine penicillin G in cows. This result should be considered when recommending milk withholding periods following the administration of penicillin by this route in lactating dairy cows.     

Gossypol pharmacokinetics in mid-lactation Brown swiss dairy cows

A bolus equivalent to 450 ppm (dosage based on average feed intake for lactating dairy cows of similar mass) of gossypol was administered orally to three Brown Swiss dairy cows in mid lactation daily for a 7-day treatment period. Blood samples were taken daily during a 2-day pretreatment period, the 7-day treatment period and a 6-day recovery period. The serum recovered from the cows was stored at -20°C until analysis for extractable gossypol content. The highest concentration of gossypol (a mean of 0.53 g/ml serum) was attained in all the cows on day 6 of the treatment period, indicating that a steady-state condition had been reached before the end of the treatment period. The gossypol concentrations then gradually declined during the 6-day recovery period but never fell to the zero baseline. The cows exhibited terminal elimination half-lives of 67, 67.5 and 40 h. Gossypol elimination was best described by a bi-exponential decay curve in two cows and a mono-exponential decay curve in the remaining cow.     

The pharmacokinetics of chloramphenicol in plasma and saliva of dairy cows

In the present study the pharmacokinetics of chloramphenicol were investigated in bovine plasma and saliva. The method of detection of chloramphenicol, a radio-immunoassay, requires only small sample volumes, no further clean-up, and a large number of samples can be processed simultaneously. This enabled the collection of a larger number of samples over a longer period of time than in previous studies. The intention was to obtain a complete pharmacokinetic profile of chloramphenicol, to evaluate it according to common open-compartment models, and to compare it with the results of previous studies. The radio-immunoassay results were confirmed by analysing a number of samples distributed over the concentration range of interest by a gas-chromatographic method with electron-capture detection. The suitability of saliva was evaluated as a possible means of monitoring compliance with the ban on chloramphenicol in the Federal Republic of Germany in milk-producing animals.     

Comparison of the pharmacokinetics of penicillin G and ampicillin in the horse.

The affinity and the binding capacity of horse serum proteins for ampicillin and penicillin G were measured by equilibrium dialysis or ultrafiltration technique. From the figures thus obtained it may be concluded that in the range of therapeutic concentrations the protein-bound fraction accounts for 6 X 8-8 per cent of the total ampicillin concentration and for 52-54 per cent of the total penicillin G concentration in serum. The rate of elimination of ampicillin and penicillin G in horses was assessed by following serum concentrations after a single intravenous injection. The biological half life of ampicillin was found to be 93 min and that of penicillin G 53 min in adult horses with unimpaired circulation and intact kidney and liver function.     

Concentrations of buparvaquone in milk and tissue of dairy cows

AIM: To determine the concentration of the anti-theilerial drug buparvaquone in the milk and tissue of dairy cattle following treatment with two different formulations, and to assess the effect of clinical theileriosis on the concentration of buparvaquone in milk.

METHODS: Healthy lactating dairy cows (n=25) were injected once (Day 0) I/M with 2.5?mg/kg of one of two formulations of buparvaquone (Butalex; n=12 or Bupaject; n=13). Milk samples were collected from all cows daily until Day 35. Five cows were slaughtered on each of Days 56, 119, 147, 203 and 328, and samples of liver, muscle and injection site tissue collected. Milk samples were also collected from cows (n=14) clinically affected with theileriosis for up to 21 days after treatment with buparvaquone. Milk and tissue samples were analysed by liquid chromatography-mass spectrometry; limits of detection (LOD) were 0.00018?mg/kg for muscle and 0.00023?mg/L for milk. Concentrations of buparvaquone in milk and tissues were log₁₀-transformed for analysis using multivariate models.

RESULTS: In healthy cows, concentrations of buparvaquone in milk declined with time post-treatment (p<0.001), but were above the LOD in 11 of 25 cows at Day 35. Concentration in milk was higher one day after treatment in cows treated with Butalex than in cows treated with Bupaject, but not different thereafter (p=0.007). Concentrations of buparvaquone in muscle were below the LOD for four of five animals at Day 119 and for all animals by Day 147, but were above the LOD at the injection site of one cow, and in the liver of three cows at Day 328. Tissue concentrations did not differ with formulation nor was there a formulation by time interaction (p>0.3).

Concentrations of buparvaquone in the milk of clinically affected animals were not different from those of healthy animals at 1 and 21 days post-treatment (p=0.72). Between 21 and 25 days post-treatment concentrations were below the LOD in 9/14 milk samples from clinically affected cows.

CONCLUSIONS: Detectable concentrations of buparvaquone were found in the milk of some cows for at least 35 days and in the liver and injection site of some cows until at least 328 days after injection. There were no biologically meaningful differences in milk or tissue concentrations between the formulations, or in the milk concentrations for cows that were clinically affected compared with those that were healthy at the time of treatment.     

SARA状态下瘤胃产生的LPS对奶牛乳腺组织细胞凋亡的影响

本试验采用12头泌乳中期的荷斯坦奶牛,随机分为两组,每组6只。其中一组饲喂低精料日粮,即日粮中含有40%的精料和60%的粗料,精粗比为4∶6,作为对照(LC)组;另外一组饲喂高精料日粮,精粗比为6∶4,作为试验(HC)组。试验周期为18周,试验开始前为所有奶牛安装瘤胃瘘管,试验后期采集瘤胃液,乳动脉、静脉血和乳腺组织样品,测定瘤胃液p H值和LPS含量、血浆中LPS含量、乳腺组织细胞中凋亡相关基因如caspase-3、caspase-8、caspase-9、bax和bcl-2等的表达、凋亡相关蛋白酶的活性和NF-κB通路中的蛋白表达。结果显示:长期高精料饲喂使奶牛瘤胃p H值均值降低,一天中p H值低于5.6的时间超过3 h;高精料组血浆和瘤胃液中LPS含量均极显著高于低精料组(P0.01);高精料组caspase-3的基因表达显著高于低精料组(P0.05),而bcl-2的基因表达显著低于低精料组(P0.05);高精料组caspase-3和caspase-8的酶活性相比于低精料组都显著升高(P0.01);高精料组NF-κB p65和磷酸化的NF-κB p65的蛋白表达量均显著高于低精料组(P0.05)。     

Effect of lameness on the calving-to-conception interval in dairy cows

OBJECTIVE: To examine the relationship between lameness and the duration of the interval from calving to subsequent conception in lactating dairy cows. DESIGN: Cohort study. ANIMALS: 837 dairy cows. PROCEDURE: Cows affected with lameness were classified into 1 of 4 groups on the basis of types of disease or lesions observed, including foot rot, papillomatous digital dermatitis, claw lesions, or multiple lesions. Cows not affected with lameness were classified as healthy. Time from calving to conception was compared between lame cows and healthy cows. RESULTS: 254 (30%) cows were affected with lameness during lactation. Most lame cows (59%) had claw lesions. Lame cows with claw lesions were 0.52 times as likely to conceive as healthy cows. Median time to conception was 40 days longer in lame cows with claw lesions, compared with healthy cows. Number of breedings per conception for lame cows with claw lesions was significantly higher than that for healthy cows. CONCLUSION AND CLINICAL RELEVANCE: Claw lesions were the most important cause of lameness, impairing reproductive performance in dairy cows, as indicated by a higher incidence of affected cows and a greater time from calving to conception and a higher number of breedings required per conception, compared with healthy cows.     

Effects of experimentally induced Streptococcus suis infection on the pharmacokinetics of penicillin G in pigs

The pharmacokinetics of potassium penicillin G were studied in both healthy (n = 8) and experimentally Streptococcus-suis-infected (n = 6) pigs following intramuscular administration (15,000 iu/kg). Streptococcus-suis infection was induced artificially in young cross-bred pigs by subcutaneous inoculation with 9 x 10(8) to 10(9) colony-forming units of S. suis. The rectal temperature of infected pigs was significantly increased (P less than 0.01) before penicillin G injection and this was maintained for 8 h after the drug was given. Other clinical symptoms were also present. The serum concentration-time data for penicillin were found to fit a one-compartment open model with first-order absorption in the two groups of pigs. Significant changes were not observed between healthy and diseased pigs in following parameters: A, Ka, Ke and Tmax. However, in diseased pigs, significant increases (P less than 0.01) were found in Vd and ClB, and significant decreases (P less than 0.01) in Cmax and AUC occurred. The increased body clearance (ClB) and greater apparent volume of distribution (Vd) of penicillin G could partly explain why the serum values of the drug were much lower in diseased pigs than in healthy pigs.     

Effect of lameness on milk yield in dairy cows

OBJECTIVE: To examine the relationship between lameness and milk yield in dairy cows. DESIGN: Cohort study. ANIMALS: 531 dairy cows. PROCEDURE: Cows affected with lameness were classified into 1 of 3 groups on the basis of type of diseases or lesions observed, including interdigital phlegmon (foot rot), papillomatous digital dermatitis (foot warts), or claw lesions. Cows not affected with lameness were classified as healthy. From Dairy Herd Improvement Association records, 305-day mature equivalent milk yield data were collected at the end of lactation or when the cow left the herd. Milk yield was compared between cows affected with lameness and healthy cows. RESULTS: 167 (31%) cows were affected with lameness during lactation. Lame cows had claw lesions (60%), papillomatous digital dermatitis (31%), or interdigital phlegmon (9%). Milk yield in lame cows with interdigital phlegmon (mean, 17,122 lb) was significantly less, compared with healthy cows (19,007 lb). CONCLUSIONS AND CLINICAL RELEVANCE: In this herd, interdigital phlegmon was associated with a 10% decrease in milk production. Lame cows with claw lesions or papillomatous digital dermatitis produced less milk than healthy cows, but the difference was not significant.     

青贮玉米秸饲喂奶牛效果研究

采用在奶牛日粮中分别加入青贮玉米秸和玉米秸对比试验的方法，经过30d锔喂试验，表明试验组比对照组日均产奶高1．24kg,差异显著（P＜0．05）。     

Clinical pharmacokinetics of carbenicillin, carfecillin, ticarcillin and BL-P 1654 in dairy cows

The minimal inhibitory concentrations (MIC) of carbenicillin, ticarcillin and BL-P 1654 for gram-negative udder pathogens were determined using the agar plate dilution method. The MIC of the drugs for 50% and 90% of the isolates examined ranged for Escherichia coli and Aerobacter spp. from 1.56 to 25 micrograms/ml, and for Klebsiella spp. and Pseudomonas spp. from 3.12 to 50 micrograms/ml. The Serratia spp. were relatively non-susceptible for the drugs studied (MIC greater than 50 micrograms/ml). Each drug was administered intravenously at 5 g and 15 g per cow to different groups of cows with normal and inflamed quarters of the udder. Distribution and elimination kinetic parameters calculated from serum drug level data were very similar to those of other beta-lactam antibiotics. Although drug concentrations in milk from inflamed quarters were higher than in milk from normal quarters, they were considerably below the MIC for the majority of gram-negative udder pathogens. The data suggest that parenteral treatment of gram-negative udder infections with carbenicillin, carfecillin, ticarcillin and BL-P 1654 at the dose levels used in the present study is unlikely to result in a bacteriological cure and would probably be clinically ineffective.     

Adipose tissue lipolysis and remodeling during the transition period of dairy cows

Elevated concentrations of plasma fatty acids in transition dairy cows are significantly associated with increased disease susceptibility and poor lactation performance. The main source of plasma fatty acids throughout the transition period is lipolysis from adipose tissue depots. During this time, plasma fatty acids serve as a source of calories mitigating the negative energy balance prompted by copious milk synthesis and limited dry matter intake.Past research has demonstrated that lipolysis in the adipose organ is a complex process that includes not only the activation of lipolytic pathways in response to neural, hormonal, or paracrine stimuli, but also important changes in the structure and cellular distribution of the tissue in a process known as adipose tissue remodeling. This process involves an inflammatory response with immune cell migration, proliferation of the cellular components of the stromal vascular fraction, and changes in the extracellular matrix. This review summarizes current knowledge on lipolysis in dairy cattle, expands on the new field of adipose tissue remodeling, and discusses how these biological processes affect transition cow health and productivity.     

Distribution of penicillin G in serum and tissue cage fluid in cattle

The penetration of penicillin into tissue cage fluid (TCF) in calves was studied after intravenous and intramuscular injection. The penicillin concentrations in TCF were lower than in serum and maximum was reached much later. Intravenous injection of benzyl-penicillin gave significantly higher levels in TCF than intramuscular injection. The penetration after procaine penicillin was very slow. The results showed that the serum peak rather than the area under curve determines the penetration of penicillin. Repeated intramuscular injections of benzylpenicillin and procaine penicillin caused an accumulation of penicillin in TCF. Similar levels were however reached by one single intravenous injection. The clinical counterparts to the used tissue cage model are abscesses. It was concluded that if high penicillin concentration are desireable in such foci, the drug must be given in a way that gives as high serum peaks as possible.     

Single-dose pharmacokinetics of oxytetracycline and penicillin G in tammar wallabies (Macropus eugenii)

McLelland, D.J., Barker, I.K., Crawshaw, G., Hinds, L.A., Spilsbury, L., Johnson, R. Single‐dose pharmacokinetics of oxytetracycline and penicillin G in tammar wallabies (Macropus eugenii). J. vet. Pharmacol. Therap. 34 , 160–167. The pharmacokinetics of oxytetracycline and penicillin G was investigated in tammar wallabies (Macropus eugenii). Groups of eight healthy tammar wallabies were administered i.v. oxytetracycline hydrochloride (40 mg/kg), i.m. long‐acting‐oxytetracycline (20 mg/kg), i.v. sodium penicillin G (30 mg/kg), or i.m. procaine/benzathine penicillin G (30 mg/kg). Plasma concentrations of oxytetracycline were determined using high‐performance liquid chromatography. Pharmacokinetic parameters were comparable to those reported for eutherians of equivalent size and suggest that the practice of adjusting allometrically scaled doses to account for the lower metabolic rate of marsupials may not be valid. Long‐acting oxytetracycline and penicillin G both demonstrated depot effects. However, the plasma concentrations achieved question the therapeutic efficacy of the long‐acting preparations.     

Effect of feeding on reproductive performance in Finnish dairy cows

The effect of 2 types of feeding on the involution of the genital tract and on the fertility was studied in 79 Finnish dairy cows on a research farm. The cows were fed twice a day with home-produced feed in accordance with the Finnish feeding standard. The cows were divided according to the type of feed into a hay-urea group and a silage group. The cows were examined clinically by rectal palpation 3 times a week during 8 weeks postpartum. The time required for the complete involution of uterus and cervix was recorded. The cows in the silage group had a significantly longer time in uterine involution, a lower fertility rate at first insemination and a longer interval from calving to conception than those in the hay-urea group. The pregnancy rate in the first insemination was in the hay-urea group 91% and in the silage group 57%. The interval between calving and the first insemination was shorter in the hay-urea group than in the silage group: 71.4 +/- 10.6 and 74.0 +/- 10.3 days, respectively. The interval between calving and conception was in the hay-urea group significantly (p less than 0.01) shorter than in the silage group; 74.8 +/- 15.1 and 89.5 +/- 24.4 days, respectively.     

Effect of melatonin on biochemical variables of the blood in dairy cows

In order to examine the effect of exogenous melatonin on selected biochemical variables of the blood in ruminants, dairy cows were given the pineal gland hormone in the dose of 0.1 mg/kg body weight. One and four hours after melatonin administration blood samples were collected from the cows in the control and the treated group in order to determine the levels of glucose, insulin, total cholesterol, triglycerides, free fatty acids, as well as the activities of alanine and aspartate aminotransferase. The pineal gland hormone caused a significant increase in the levels of total cholesterol and triglycerides, slight increases in glucose and insulin levels, and a significant decrease in the concentration of free fatty acids. Melatonin did not exert an effect on the activity of liver enzymes.     

Effect of beta-carotin serum concentration on the reproductive performance in dairy cows

The aim of the following investigation was to study the effect of beta-carotin serum concentrations on reproductive performance in dairy cows. Blood samples were collected from 201 cows 3 to 4 weeks antepartum, 1 to 2 weeks postpartum and at the time of insemination. Concentrations of beta-carotin in blood serum were determined via HPLC. The incidence of retained placental fetal membranes, endometritis, ovarian cysts as well as the beginning of the oestrous cycle and various measures of fertility such as first service conception rate, pregnancy index, interval from calving to first insemination, interval from calving to conception, interval from first insemination to conception and expected calving interval were recorded and analysed. The beta-carotin serum concentrations were not related to the incidence of retained placental fetal membranes, endometritis, ovarian cysts or the onset of cyclicity post partum. Cows with lower beta-carotin concentrations partially seemed to have a reduced reproductive performance than cows with higher beta-carotin concentrations. Overall, our results suggest only a minor relationship between the beta-carotin serum concentration and fertility in dairy cows.