Pharmacokinetics of florfenicol in veal calves

The pharmacokinetic disposition of florfenicol was described in veal calves after administration of a single 22-mg/kg dose intravenously, orally after a 12-h fast and orally 5 min post feeding. Both serum concentrations and urinary excretion were studied. After intravenous administration the median elimination half-life was 171.9 min while the half-life of the distribution phase was 5.9 min. The median body clearance (Cl) and apparent volume of distribution (Vz) were 2.85 ml/kg/min and 0.78 l/kg, respectively. Following oral administration the median bio-availability (f) was 0.88 for calves dosed after a 12-h fast and 0.65 for calves dosed 5 min post feeding. Calves given the oral doses had a complex absorption pattern with delayed absorption. Slightly more than 50% of the administered dose both orally and intravenously was recovered as unchanged florfenicol in the urine by 30 h.     

Salmonellosis in veal calves. Some therapeutic aspects

Summary

The present investigation was undertaken to improve regimens dosage of amoxycillin, chloramphenicol or trimethoprim‐sulphadiazine in Salmonella dublin infected veal calves. The pharmacokinetics of these drugs were studied after i.v., oral, and i. m. administration (bioavailability, local irritation at the injection site, volume of distribution, and elimination half life). The most important conclusion was that amoxycillin, chloramphenicol, and trimethoprim were suitable for oral administration to veal calves, although the bioavailability of chloramphenicol and trimethoprim was significantly less when concurrently administered with a milk replacer. In vitro, the antibacterial activities of these drugs were compared. Addition of trimethoprim to sulphadiazine lowered its MIC for S. dublin, but sulphadiazine reduced the killing rate compared to that of trimethoprim alone. In the efficacy studies the activities of several serum enzymes and the plasma concentrations of Fe, Zn, and Cu were measured, but it appeared, that these biochemical parameters were no better than the clinical parameters body temperature and body weight. Using optimal dosage regimens based on MIC values and blood levels, treatment with either of the three drugs was of equal efficacy.     

Salmonellosis in veal calves. Some therapeutic aspects

The present investigation was undertaken to improve regimens dosage of amoxycillin, chloramphenicol or trimethoprim-sulphadiazine in Salmonella dublin infected veal calves. The pharmacokinetics of these drugs were studied after i.v., oral, and i.m. administration (bioavailability, local irritation at the injection site, volume of distribution, and elimination half life). The most important conclusion was that amoxycillin, chloramphenicol, and trimethoprim were suitable for oral administration to veal calves, although the bioavailability of chloramphenicol and trimethoprim was significantly less when concurrently administered with a milk replacer. In vitro, the antibacterial activities of these drugs were compared. Addition of trimethoprim to sulphadiazine lowered its MIC for S. dublin, but sulphadiazine reduced the killing rate compared to that of trimethoprim alone. In the efficacy studies the activities of several serum enzymes and the plasma concentrations of Fe, Zn, and Cu were measured, but it appeared, that these biochemical parameters were no better than the clinical parameters body temperature and body weight. Using optimal dosage regimens based on MIC values and blood levels, treatment with either of the three drugs was of equal efficacy.     

Pharmacokinetics, metabolism and renal clearance of flumequine in veal calves

The pharmacokinetics of flumequine was studied in 1-, 5- and 18-week-old veal calves. A two-compartment model was used to fit the plasma concentration-time curve of flumequine after the intravenous injection of 10 mg/kg of a 10% solution. The elimination half-life (t1/2 beta) of the drug ranged from 6 to 7 h. The Vd beta and ClB of 1-week-old calves (1.07 l/kg, 1.78 ml/min/kg) were significantly lower than those of 5-week-old (1.89 l/kg, 3.23 ml/min/kg) and 18-week-old calves (1.57 l/kg, 3.10 ml/min/kg). After the oral administration of 10 mg/kg of a 2% flumequine formulation mixed with milk replacer, the Cmax was highest in 1-week-old (9.27 micrograms/ml) and lowest in 18-week-old calves (4.47 micrograms/ml). The absorption was rapid (Tmax of approximately 3 h) and complete. When flumequine itself and a formulation containing 2% flumequine and 20 X 10(6) iu of colistin sulphate were mixed with milk replacer and administered at the same dose rate, absorption was incomplete and Cmax was lower. The main urinary metabolite of flumequine was the glucuronide conjugate (approximately 40% recovery within 48 h of intravenous injection) and the second most important metabolite was 7-hydroxy-flumequine (approximately 3% recovery within 12 h of intravenous injection). Only 3.2-6.5% was excreted in the urine unchanged. After oral administration a 'first-pass' effect was observed, with a significant increase in the excretion of conjugated drug. For 1-week-old calves it is recommended that the 2% formulation should be administered at a dose rate of 8 mg/kg every 24 h or 4 mg/kg every 12 h; for calves over 6 weeks old, the dose should be increased to 15 mg/kg every 24 h or 7.5 mg/kg every 12 h. The formulation containing colistin sulphate should be administered to 1-week-old calves at a flumequine dose of 12 mg/kg every 24 h or 6 mg/kg every 12 h.     

Copper toxicosis in veal calves

Copper toxicosis was diagnosed in 7 veal calves, 10-16 weeks old, from 5 separate farms. All calves died without specific clinical signs, although 4 of the calves were icteric. The calves' dietary rations had been supplemented with various copper-containing hematinics. Peritoneal hemorrhage was reported at post-mortem in 2 calves. Microscopic evidence of hepatopathy consisted of hepatocellular degeneration and necrosis, hemorrhage, and fibrosis. Concentrations of copper in livers from intoxicated calves ranged from 277 to 684 ppm and in kidneys from 1.1 to 82.0 ppm. The extent and severity of lesions in livers appeared to correlate with concentrations of copper. Nephrosis was minimal, without evidence of hemoglobinuria.     

Three phase elimination of oxytetracycline in veal calves; the presence of an extended terminal elimination phase

The pharmacokinetics of oxytetracycline were studied after both intravenous (i.v.) and intramuscular (i.m.) administration to a group of five veal calves. Blood samples were taken frequently during the terminal elimination phase in order to calculate a reliable elimination rate constant. Because of the low limit of quantification of the method of analysis used, oxytetracycline plasma concentrations could be monitored over a 12-day period of time.
After the intravenous administration of oxytetracycline, data were fitted according a three-compartment model. After i.m. administration, plasma-concentration-time curves could best be described by a two-compartment model. It was demonstrated that a very slow terminal elimination phase was present both after i.v. and i.m. administration with a half-life of approximately 95 h. The data show that this phase cannot be explained by slow absorption from the injection site and that release of oxytetracycline incorporated into bone is not a likely explanation.     

Transportation of veal calves in Switzerland

The analysis and optimization of transportation routes of calves to slaughterhouses by means of a GIS (geographical information system) route planning and time limitation software for the fleet management in transportation industry was performed. As basic data the farms (last locations of the calves) and the slaughterhouses were available in each case with addresses and coordinates. 150 data records from 258 veal calves could be evaluated. None of the calves was transported longer than 6 hours. Therefore, in all cases the Swiss law for animal protection was obeyed concerning maximum length of transportation time. In the road model, 82% of calves were transported too far.     

Effects of anabolic and therapeutic doses of dexamethasone on thymus morphology and apoptosis in veal calves

Three groups of 10 veal calves were treated, respectively, with 5 mg of dexamethasone-21-isonicotinate administered intramuscularly on days 0 and 7 (group A); 0.4 mg/day of dexamethasone-21-phosphate administered orally for 20 days (group B); or left untreated as controls (group C). Two animals from each group were slaughtered on day 3, 7, 14, 32 and 52. The size and weight of the thymus decreased progressively in both treated groups until day 32. On day 14, in comparison with the controls, there was a mean reduction of 76 per cent in the thymus weight of group A and 35 per cent in group B. On day 32, the reductions were 13 per cent in group A and 50 per cent in group B, but the thymus weight of both groups had recovered completely by day 52. Dexamethasone-induced changes in thymus weight associated with lymphoid depletion and fat replacement, and there were clear correlations between these changes and apoptosis of thymocytes.     

Oral absorption and bioavailability of flumequine in veal calves

Summary

The oral absorption and bioavailability of flumequine was studied in 1‐, 5‐ and 18‐week‐old calves following intravenous and oral administration of different formulations of flumequine (Flumix^®, Flumix C^® and pure flumequine). Increasing age had a negative influence on the C_max after the administration of Flumix^®, based on a larger V_D in the older calves. The C_max decreased from 5.02 ± 1.46 μg/ml in the first week to 3.28 ± 0.42 μg/ml in the 18th week. Adding colistin sulfate to the flumequine formulation and administring pure flumequine mixed with milk replacer had a negative effect on the C_max of flumequine after oral administration of 5 and 10 mg/kg body weight. The bioavailability of the orally administered flumequine formulations was 100% in all cases except after the administration of Flumix C^®, for which it was 75.9 ± 18.2%. The urinary recovery of flumequine after intravenous injection of a 10% solution varied from 35.2 ± 2.3% for Group B. to 41.2 ± 6.3% for Group C.

The dosage of 5 mg/kg body weight Flumix^® twice daily in 1‐week‐old veal calves is sufficient to reach therapeutic plasma concentrations, based on a MIC value of 0.8 μg/ml of the target bacteria.

In older calves it is advisable to increase the dosage 7.5 or 10 mg/kg body weight every 12 hours. In combination with colistin sulfate it is also advisable to increase the dosage slightly because of the negative effect of the colistin sulfate on the C_max of flumequine.     

Oral absorption and bioavailability of flumequine in veal calves

The oral absorption and bioavailability of flumequine was studied in 1-, 5- and 18-week-old calves following intravenous and oral administration of different formulations of flumequine (Flumix, Flumix C and pure flumequine). Increasing age had a negative influence on the Cmax after the administration of Flumix, based on a larger VD in the older calves. The Cmax decreased from 5.02 +/- 1.46 micrograms/ml in the first week to 3.28 +/- 0.42 micrograms/ml in the 18th week. Adding colistin sulfate to the flumequine formulation and administring pure flumequine mixed with milk replacer had a negative effect on the Cmax of flumequine after oral administration of 5 and 10 mg/kg body weight. The bioavailability of the orally administered flumequine formulations was 100% in all cases except after the administration of Flumix C, for which it was 75.9 +/- 18.2%. The urinary recovery of flumequine after intravenous injection of a 10% solution varied from 35.2 +/- 2.3% for Group B, to 41.2 +/- 6.3% for Group C. The dosage of 5 mg/kg body weight Flumix twice daily in 1-week-old veal calves is sufficient to reach therapeutic plasma concentrations, based on a MIC value of 0.8 micrograms/ml of the target bacteria. In older calves it is advisable to increase the dosage 7.5 or 10 mg/kg body weight every 12 hours. In combination with colistin sulfate it is also advisable to increase the dosage slightly because of the negative effect of the colistin sulfate on the Cmax of flumequine.     

A survey of abomasal ulceration in veal calves

Abomasal ulceration was found in 264 of 304 commercially reared veal calves at slaughter. The incidence and severity of lesions were greatest in loose housed calves with access to straw and fed milk substitute ad libitum. The majority of lesions were located in the distal pylorus. There was no evidence that the abomasal erosions and ulcers found in the majority of veal calves affected their growth rate or were deleterious to their welfare. It is suggested that pyloric ulceration may be related to the diet of veal calves.     

Relative bioavailability of microgranulated sulfadimidine in veal calves

The kinetics of free and microgranulated sulfadimidine were compared in milk-fed calves dosed orally (180 mg/kg) in a crossover study. Microgranulation results in delayed absorption of sulfadimidine and poor bioavailability, with the area under the plasma concentration-time curve ( AUC (O-oo)) reduced from 7400 to 3781 μg·h/mL, and maximum plasma concentration ( C _max) reduced from 188.1 ± 39.0 to 84.41 ± 22.6 μg/mL. It is concluded that sulfadimidine microgranulated with long chain fatty acids is not suitable for use in milk-fed calves; the gastrointestinal transit time is too rapid to allow full release of the drug, markedly limiting its bioavailability. In adult animals, or in the young of other animal species in which digesta transit time is slower than in calves, the bioavailability of microgranulated sulfadimidine may be much greater.     

Penetration of oxytetracycline into tissue-cages in calves

Concentrations of oxytetracycline (OTC) in serum and tissue-cage fluid (TCF) from subcutaneous tissue-cages were determined after single and repeated intravenous and intramuscular doses of 10 mg/kg to calves. Intravenous administration resulted in higher levels, and greater area under curve (AUC) in TCF, than did intramuscular administration. However, the penetration measured as the ratio of AUC in TCF to AUC in serum was equal, and therefore independent of the route of administration. A linear relationship between AUC in serum and AUC in TCF could be demonstrated. Half-lives of OTC in serum were 4.9 +/- 3.1 h after intravenous, and 6.1 +/- 2.0 h after intramuscular administration. In TCF the half-lives were 21.5 +/- 4.4 h and 24.5 +/- 11.5 h after intravenous and intramuscular administration, respectively. Repeated dosing resulted in accumulation of OTC in TCF. Lesser accumulation in older cages indicated altered characteristics of the cages with the passage of time. In serum, no substantial accumulation was seen after repeated i.v. dosing until the dosing interval was shortened to 6 h.     

Pharmacokinetics of oxytetracycline hydrochloride in rabbits

Pharmacokinetics of oxytetracycline HCl (OTC) was studied in rabbits. After 10 mg of OTC/kg of body weight was administered IV, the distribution half-life was 0.06 hour, terminal half-life was 1.32 hours, volume of distribution area was 0.861 L/kg, and total body clearance was 0.434 L/kg/h. After 10 mg of OTC/kg was given IM, the absorption half-life was 2.09 hours, extent of absorption was 71.4%, and total body clearance of the absorbed fraction was 0.576 L/kg/h. Based on these kinetic data, a dosage of 15 mg of OTC/kg, every 8 hours was developed. This dose given IM for 7 consecutive days resulted in observed steady-state maximum and minimum concentrations (mean +/- SD) of 4.7 +/- 0.3 micrograms/ml and 3.2 +/- 0.6 micrograms/ml, respectively. Twice this dose (30 mg of OTC/kg, every 8 hours) given IM caused anorexia and diarrhea.     

Enteric infections in veal calves: A longitudinal study on four veal calf units

Summary

Forty‐five calves on four veal calf units were monitored during the first four weeks after their arrival. Faecal samples were collected on alternate days and screened for the presence of rotaviruses, bovine coronavirus, Cryptosporidium oocysts, K99 positive strains of E. coli and Salmonella spp. Rotaviruses and Cryptosporidium were the most commonly detected agents (78% and 60% respectively of the calves). Bovine coronavirus was detected in the faeces of 18% of the calves, whilst K99 positive E. coli was only found in 2 samples from one calf. Salmonella spp. were not isolated from any of the 646 faecal samples examined. Shedding of rotaviruses occurred in a bimodal pattern beginning in the first week of the survey. Cryptosporidium oocysts were detected most frequently in the interval between the two peaks of rotavirus shedding. The presence of rotaviruses or Cryptosporidium oocysts in faeces was not strongly associated with scour, nor were combined infections with these agents or the cases of bovine coronavirus infection. The condition of the calves throughout the survey was generally satisfactory.     

The pharmacokinetics and residues of clenbuterol in veal calves.

Seven female Brown Swiss calves were used to study the pharmacokinetics of clenbuterol after an effective anabolic dosage of 5 micrograms/kg of BW was given twice daily for 3 wk. Analyses of clenbuterol concentrations in different tissues was done by enzyme immunoassay (EIA). Tissue samples were taken from three calves on the last day of administration and from two more after 3.5 or 14 d of clenbuterol withdrawal. The rate of clenbuterol elimination was dependent on time and tissue. Clenbuterol concentrations in the lung dropped from a mean of 76 ng/g to a level of less than .08 ng/g after 14 d, whereas in the liver the clenbuterol concentrations decreased from 46 ng/g to .6 ng/g within 14 d of withdrawal. Highest levels were always found in the eye: 118 ng/g, 57.5 ng/g, and 15.1 ng/g after 0, 3.5, and 14 d of withdrawal, respectively. These data reveal that different compartments contribute to the elimination of clenbuterol; therefore, concentrations in urine do not follow first order kinetics. An initial rapid decline in the concentration of clenbuterol in urine with a half-life of 10 h is followed by a slower elimination with a half-life of about 2.5 d. Treatments using the anabolic dose of 5 micrograms/kg of BW require longer withdrawal times than the therapeutic dose (.8 micrograms/kg BW).     

Enteric infections in veal calves: a longitudinal study on four veal calf units

Forty-five calves on four veal calf units were monitored during the first four weeks after their arrival. Faecal samples were collected on alternate days and screened for the presence of rotaviruses, bovine coronavirus, Cryptosporidium oocysts, K99 positive strains of E. coli and Salmonella spp. Rotaviruses and Cryptosporidium were the most commonly detected agents (78% and 60% respectively of the calves). Bovine coronavirus was detected in the faeces of 18% of the calves, whilst K99 positive E. coli was only found in 2 samples from one calf. Salmonella spp. were not isolated from any of the 646 faecal samples examined. Shedding of rotaviruses occurred in a bimodal pattern beginning in the first week of the survey. Cryptosporidium oocysts were detected most frequently in the interval between the two peaks of rotavirus shedding. The presence of rotaviruses or Cryptosporidium oocysts in faeces was not strongly associated with scour, nor were combined infections with these agents or the cases of bovine coronavirus infection. The condition of the calves throughout the survey was generally satisfactory.     

Pathology and residues in veal calves treated experimentally with clenbuterol

Six veal calves were medicated with clenbuterol at 20 μg kg bodyweight⁻¹ day⁻¹ for 42 days before they were slaughtered, to evaluate the lesions and residues in target organs. Compared with six unmedicated calves the most noticeable changes were tracheal dilatation, decreased uterine weight, slight mucous hypersecretion in the uterus and vagina and depletion of liver glycogen. The highest concentrations of clenbuterol (62 to 128 ng/g⁻¹) were recorded in the choroid/retina, and the aqueous humour had the lowest concentration (0·5 to 2·4 ng ml⁻¹). The residue concentrations were higher than the maximum residue level set for clenbuterol (0·5 ng g⁻¹)