Cardiovascular effects of intravenous administration of tetracycline in cattle

Tetracycline chloride dissolved in saline was injected intravenously to seven cows. Two doses of tetracycline were used: 5 and 10 mg/kg b.wt, and the injections were given over a period of either 10, 60 or 300 sec.
A number of the cows collapsed shortly after the injection was completed, usually when the 10 mg dosage was given in 60 sec. When the same dose was given over a period of 5 min none of the cows collapsed. A more or less pronounced drop in blood pressure could be detected during or shortly after the injection; in those cows which collapsed the blood pressure fell almost to zero. The predominant change in pulse rate in connection with the tetracycline administration was a decrease which could be quite marked, pulse rates falling as low as 10–20 per min. Simultaneously with these changes in blood pressure and pulse rate severe abnormalities in ECG could be observed. Pre-treatment with a normal therapeutic dose of calcium borogluconate intravenously prevented collapse in the cows and diminished the drop in blood pressure associated with an ensuing tetracycline injection.
It is concluded that intravenous injection of tetracycline is hazardous, but that collapse can be avoided by giving the injection very slowly over a period of no less than 5 min.     

Cardiovascular effects and fatalities associated with intravenous administration of doxycycline to horses and ponies.

Intravenous use of doxycycline in horses is associated with deleterious side effects on the cardiovascular system which may result in fatalities. At dosages and infusion rates used in these studies, supraventricular tachycardia, systemic arterial hypertension, clinical signs of discomfort, collapse and death were observed. Results of the present study suggest that the intravenous use of doxycycline should be avoided in horses.     

Pharmacokinetic study of neomycin in calves following intravenous and intramuscular administration.

Neomycin sulfate was administered to calves by the intravenous and intramuscular routes. Serum drug levels were determined and the intravenous pharmacokinetic parameters derived using the Gauss-Newton nonlinear fitting algorithm and the two compartment open model. The kinetic parameters determined were as follows: zero time intercept, serum drug level 68.045 +/- 15.894 micrograms/mL, alpha slope intercept 37.666 +/- 13.874 micrograms/mL and beta slope intercept 30.379 +/- 12.638 micrograms/mL; equilibration rate (pool I and II) 0.081 +/- 9.064 min-1; elimination rate 0.004 +/- 0.001 min-1; half-time alpha 14.774 +/- 11.236 min, half-time beta 166.596 +/- 47.576 min; first order elimination constant 0.009 +/- 0.002 min+; transfer rate constants, central to peripheral, 0.032 +/- 0.026 min+ and peripheral to central 0.045 +/- 0.037 min-1; volume of central compartment 0.186 +/- 0.047 L/kg; volume of distribution 0.388 +/- 0.130 L/kg; body clearance 0.002 +/- 0.001 L/kg/min.     

The pharmacokinetics of oxytetracycline following intravenous administration in healthy and diseased pigs

Pijpers, A., Schoevers, E.J., van Gogh, H., van Leengoed, L.A.M.G., Visser, I.J.R., van Miert, A.S.J.P.A.M. & Verheijden, J.H.M. The pharmacokinetics of oxytetracycline following intravenous administration in healthy and diseased pigs. J. vet. Pharmacol. Therap. 13, 320–326.
The pharmacokinetics of oxytetracycline (OTC) were studied in healthy pigs and in pigs endobronchially inoculated with Actinobacillus pleuropneumoniae toxins. In two groups of seven pigs OTC was administered intravenously in a single dose of 10 or 50 mg/kg, respectively. OTC was administered to clinically healthy pigs and 7 days later at 3 h after a challenge with A. pleuropneumoniae toxins. Pneumonia developed in toxin-treated pigs. In the challenged pigs there was a decreased distribution-rate constant (α) and a significantly increased elimination-rate constant (ß) ( P <0.05). Moreover, the apparent volume of distribution (V_dß) was decreased. The elimination half-lives (t_1/2ß) were approximately 6 h in the healthy pigs and 5 h in the diseased animals. There was no difference in the pharmacokinetic profile of OTC following administration of 50 mg/kg compared to 10 mg/kg.
A. Pijpers, Department of Herd Health and Reproduction, PO Box 80.151, 3508 TD Utrecht, The Netherlands.     

Cardiovascular effects of sevoflurane in Holstein calves

Objective The purpose of this study was to determine the cardiovascular effects of sevoflurane in calves. Study design Prospective experimental study. Animals Six, healthy, 8–12‐week‐old Holstein calves weighing 80 ± 4.5 (mean ± SEM) kg were studied. Methods Anesthesia was induced by face‐mask administration of 7% sevoflurane in O₂. Calves tracheae were intubated, placed in right lateral recumbency, and maintained with 3.7% end‐tidal concentration sevoflurane for 30 minutes to allow catheterization of the auricular artery and placement of a Swan‐Ganz thermodilution catheter into the pulmonary artery. After instrumentation, administration of sevoflurane was temporarily discontinued until mean arterial pressure was > 100 mm Hg. Baseline values were recorded and the vaporizer output increased to administer 3.7% end‐tidal sevoflurane concentration. Ventilation was controlled to maintain normocapnia. The following were recorded at 5, 10, 15, 30 and 45 minutes after collection of baseline data and expressed as the mean value (± SEM): direct systolic, diastolic, and mean arterial blood pressures; cardiac output; mean pulmonary arterial pressure; pulmonary arterial occlusion pressure, heart rate; and pulmonary arterial temperature. Cardiac index and systemic and pulmonary vascular resistance values were calculated using standard formulae. Arterial blood gases were analyzed at baseline, and at 15 and 45 minutes. Differences from baseline values were determined using one‐way analysis of variance for repeated measures with post‐hoc differences between mean values identified using Dunnet's test (p < 0.05). Results Mean time from beginning sevoflurane administration to intubation of the trachea was 224 ± 9 seconds. The mean end‐tidal sevoflurane concentration at baseline was 0.7 (± 0.11)%. Sevoflurane anesthesia was associated with decreased arterial blood pressure at all sampling times. Mean arterial blood pressure decreased from a baseline value of 112 ± 7 mm Hg to a minimum value of 88 ± 4 mm Hg at 5 minutes. Compared with baseline, arterial pH was decreased at 15 minutes. Pulmonary arterial blood temperature was decreased at 15, 30 and 45 minutes. Arterial CO₂ tension increased from a baseline value of 43 ± 3 to 54 ± 4 mm Hg (5.7 ± 0.4 to 7.2 ± 0.3 kPa) at 15 minutes. Mean pulmonary arterial pressure was increased at 30 and 45 minutes. Pulmonary arterial occlusion pressure increased from a baseline value of 18 ± 2 to 23 ± 2 mm Hg at 45 minutes. There were no significant changes in other measured variables. All calves recovered from anesthesia uneventfully. Conclusion We conclude that sevoflurane for induction and maintenance of anesthesia was effective and reliable in these calves and that neither hypotension nor decreased cardiac output was a clinical concern. Clinical relevance Use of sevoflurane for mask induction and maintenance of anesthesia in young calves is a suitable alternative to injectable and other inhalant anesthetics.     

Pharmacokinetics and renal clearance of oxytetracycline in piglets following intravenous and oral administration

The pharmacokinetics of oxytetracycline (OTC) in three weaned piglets was studied following three routes of administration: intravenously, orally as drench, both at a dose of 20 mg/kg, and orally as medicated (400 ppm OTC) pelleted feed administered during 3 consecutive days. Analysis of the intravenous data according to the three compartment pharmacokinetic model revealed that OTC was well distributed in the body (Vf: 1.62 l/kg), had an overall body clearance of 0.25 litre/kg/h, and the elimination half-lives were in the range between 11.6 and 17.2 hrs. The mean OTC binding to plasma proteins was 75.5 +/- 4%. Following the drench route of administration the maximum plasma OTC concentration was achieved between 1 and 5 h post application and ranged between 1.18 and 1.41 micrograms/ml. The mean maximum plasma OTC concentration during medicated feed administration was 0.20 +/- 0.06 microgram/ml, which was achieved approximately 30 hours after the onset of the administration. A steady state OTC plasma level (approximately 0.2 microgram/ml) was maintained till the end of the trial. Within 48 hours after cessation of medicated feed administration the plasma OTC levels were beneath 0.06 microgram/ml. The mean OTC bioavailabilities of the oral routes were low: after the drench route of administration 9.0 +/- 0.67%, and after medicated pelleted feed administration 3.69 +/- 0.8%. The mean OTC renal clearances of each piglet ranged between 10.1 and 13.9 ml/min/kg (based on free OTC plasma fractions). The renal OTC clearance values were urine flow dependent in all piglets and significantly correlated with the renal creatinine clearance (P less than 0.005), being 3-5 times higher than the latter. It is concluded that in piglets OTC is excreted mainly by glomerular filtration and partly by tubular secretion. The potential clinical efficacy of 400 ppm OTC as medicated feed with respect to treatment, e.g. atrophic rhinitis, is discussed.     

Pharmacokinetics and renal clearance of oxytetracycline in piglets following intravenous and oral administration

Summary

The pharmacokinetics of oxytetracycline (OTC) in three weaned piglets was studied following three routes of administration: intravenously, orally as drench, both at a dose of 20 mg/kg, and orally as medicated (400 ppm OTC) pelleted feed administered during 3 consecutive days. Analysis of the intravenous data according to the three compartment pharmacokinetic model revealed that OTC was well distributed in the body (Vie 1.621/kg), had an overall body clearance of 0.25 litre/kg/h, and the elimination half‐lives were in the range between 11.6 and 17.2 hrs.

The mean OTC binding to plasma proteins was 75.5 ± 4%. Following the drench route of administration the maximum plasma OTC concentration was achieved between 1 and 5 h post application and ranged between 1.18 and 1.41 μg/ml. The mean maximum plasma OTC concentration during medicated feed administration was 0.20 ± 0.06 μg/ml, which was achieved approximately 30 hours after the onset of the administration. A steady state OTC plasma level (approximately 0.2 μg/ml) was maintained till the end of the trial. Within 48 hours after cessation of medicated feed administration the plasma OTC levels were beneath 0.06 μg/ml. The mean OTC bioavailabilities of the oral routes were low: after the drench route of administration 9.0 ± 0.67%, and after medicated pelleted feed administration 3.69 ± 0.8%.

The mean OTC renal clearances of each piglet ranged between 10.1 and 13.9 ml/min/kg (based on free OTC plasma fractions). The renal OTC clearance values were urine flow dependent in all piglets and significantly correlated with the renal creatinine clearance (P< 0.005), being 3–5 times higher than the latter. It is concluded that in piglets OTC is excreted mainly by glomerular filtration and partly by tubular secretion. The potential clinical efficacy of 400 ppm OTC as medicated feed with respect to treatment, e.g. atrophic rhinitis, is discussed.     

Experimental chloramphenicol intoxication in neonatal calves: intravenous administration

Chloramphenicol was administered intravenously for eight to 17 days to five newborn calves at a daily dosage of 100 mg kg-1. Haemodynamic, haematological, blood chemistry, serum enzyme, urinalysis and clinical responses were evaluated. High levels of serum chloramphenicol were observed throughout the study although a marked increase in elimination rate was seen with increasing age. The most severe adverse effects were severe hypotension following rapid intravenous administration and severe gastrointestinal dysfunction with diarrhoea accompanying prolonged high dosage. There appeared to have been a haematological effect in one calf, but it was of minor significance compared with the other effects.     

Biliary elimination kinetics and tissue concentrations of oxytetracycline after intravenous administration in hens

The pharmacokinetics of the biliary elimination of oxytetracycline (OTC) and tissue concentrations in certain organs were studied in 10 Leghorn hens. The animals were anaesthetized using xylazine/ketamine administered by the intramuscular (i.m.) route and were immobilized for right laparotomy. Both bile ducts were cannulated and a dose of 20 mg/kg of oxytetracycline hydrochloride was administered intravenously (i.v.). Samples of bile excreted were taken at predetermined intervals during 6 h. At 6 h animals were slaughtered and tissue samples of blood, liver, kidney, pancreas, spleen, heart, lung and pectoral muscle were taken. The values for OTC biliary elimination rate times were best fitted to a one-exponential equation. The maximum value for OTC biliary excretion rate (3.69+/-0.6 microg/min/kg) was reached at approximately 17.5 min (time to maximum concentration (tmax)). The first-order rate constant for the biliary excretion (k) and the half-life (t1/2) were 6.7x10(-3) min(-1) and 110.55 min, respectively. The mean value of area under the biliary excretion rate time curve (AUC) indicated that 839.77 microg/kg body weight (b.w.) were eliminated by the biliary route. The cumulative biliary excretion data indicated that approximately 4.20% of the dose was eliminated by this route, 3.28% being eliminated during the first 6 h and 0.92% thereafter. The highest mean concentrations were found in the kidney (35.82 microg/kg) and liver (16.77 microg/g). Significant differences were found between the concentrations of the various tissues studied. Plasma concentration was lower than that of the other tissues (except lung).     

Cardiovascular effects of desflurane in mechanically ventilated calves

OBJECTIVE: To determine cardiovascular effects of desflurane in mechanically ventilated calves. ANIMALS: 8 healthy male calves. PROCEDURE: Calves were anesthetized by face mask administration of desflurane to permit instrumentation. Administration of desflurane was temporarily discontinued until mean arterial blood pressure increased to >or= 100 mm Hg, at which time baseline cardiovascular values, pulmonary arterial temperature, end-tidal CO(2) tension, and end-tidal desflurane concentration were recorded. Cardiac index and systemic and pulmonary vascular resistances were calculated. Arterial blood gas variables were measured and calculated. Mean end-tidal concentration of desflurane at this time was 3.4%. After collection of baseline values, administration of 10% end-tidal concentration of desflurane was resumed and calves were connected to a mechanical ventilator. Cardiovascular data were collected at 5, 10, 15, 30, and 45 minutes, whereas arterial blood gas data were collected at 15 and 45 minutes after collection of baseline data. RESULTS: Mean +/- SD duration from beginning desflurane administration to intubation of the trachea was 151 +/- 32.8 seconds. Relative to baseline, desflurane anesthesia was associated with a maximal decrease in arterial blood pressure of 35% and a decrease in systemic vascular resistance of 34%. Pulmonary arterial blood temperature was decreased from 15 through 45 minutes, compared with baseline values. There were no significant changes in other measured variables. All calves recovered from anesthesia without complications. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of desflurane for induction and maintenance of general anesthesia in calves was smooth, safe, and effective. Cardiopulmonary variables remained in reference ranges throughout the study period.     

The pharmacokinetics of primaquine in calves after subcutaneous and intravenous administration

The pharmacokinetics of primaquine was studied in calves of 180–300 kg live weight. Primaquine was injected at 0.29 mg/kg (0.51 mg/kg as primaquine diphosphate) intravenously (IV) or subcutaneously (SC) and the plasma concentrations of primaquine and its metabolite carboxyprimaquine were determined by high-performance liquid chromatography. The extrapolated concentration of primaquine at zero time after IV administration was 0.50±0.48 µg/ml (mean ±SD) which decreased with an elimination half-life of 0.16±0.07 h. Primaquine was rapidly converted to carboxyprimaquine after either route of administration. The peak concentration of carboxyprimaquine was 0.50±0.08 µg/ml at 1.67±0.15 h after IV administration. The corresponding value was 0.47±0.07 µg/ml at 5.05±1.20 h after SC administration. The elimination half-lives of carboxyprimaquine after IV and SC administration were 15.06±0.99 and 12.26±3.06 h, respectively. The areas under the concentration-time curve for carboxyprimaquine were similar following either IV or SC administration of primaquine; the values were 11.85±2.62 µg.h/ml after the former and 10.95±2.65 µg.h/ml after the latter. The mean area under the concentration-time curve for primaquine was less than 0.1 µg.h/ml after either route of administration.Abbreviations AUC area under the concentration-time curve - CPRQ carboxyprimaquine - IV intravenous - 6M8AQ 6-methoxy-8-aminoquinoline - PRQ primaquine - SC subcutaneous     

Pharmacokinetics of firocoxib in preweaned calves after oral and intravenous administration

The objective of this study was to determine the pharmacokinetics of intravenous and oral firocoxib in 10 healthy preweaned calves. Firocoxib (0.5 mg/kg) was initially administered i.v. to calves, and following a 14‐day washout period, animals received firocoxib orally prior to cautery dehorning. Firocoxib concentrations were determined by liquid chromatography–tandem mass spectrometry. Changes in hematology and plasma chemistry were determined using automated methods. Computer software was used to estimate pharmacokinetic parameters best described with a two‐compartment model for i.v. administration and a one‐compartment model for p.o. administration. Following i.v. dosing, the geometric mean (range) T_1/2K10 and T_1/2β were 6.7 (4.6–9.7) and 37.2 (23.5–160.4) h, respectively, V_ss was 3.10 (2.10–7.22) L/kg, and CL was 121.7 (100.1–156.7) mL/h/kg. Following oral administration, geometric mean (range) C_max was 127.9 (102.5–151.3) ng/mL, T_max was 4.0 (2.6–5.6) h, and T_1/2K10 was 18.8 (14.2–25.5) h. Bioavailability of oral firocoxib was calculated using the AUC derived from both study populations to be 98.4% (83.1–117.6%). No adverse clinical effects were evident following firocoxib administration. Pharmacokinetic analysis of i.v. and p.o. firocoxib indicates high bioavailability and a prolonged terminal half‐life in preweaned calves.     

Pharmacokinetics following intravenous administration and pharmacodynamics of cefquinome in buffalo calves

Disposition following single intravenous injection (2 mg/kg) and pharmacodynamics of cefquinome were investigated in buffalo calves 6–8 months of age. Drug levels in plasma were estimated by high-performance liquid chromatography. The plasma concentration–time profile following intravenous administration was best described by a two-compartment open model. Rapid distribution of cefquinome was evident from the short distribution half-life (t _½α ?=?0.36?±?0.01 h), and small apparent volume of distribution (Vd_area?=?0.31?±?0.008 L/kg) indicated limited drug distribution in buffalo calves. The values of area under plasma concentration–time curve, elimination half-life (t _½β ), total body clearance (Cl_B), and mean residence time were 32.9?±?0.56 μg·h/mL, 3.56?±?0.05 h, 60.9?±?1.09 mL/h/kg, and 4.24?±?0.09 h, respectively. Minimum inhibitory concentration (MIC) and minimum bactericidal concentration of cefquinome were 0.035–0.07 and 0.05–0.09 μg/mL, respectively. A single intravenous injection of 2 mg/kg may be effective to maintain the MIC up to 12 h in buffalo calves against the pathogens for which cefquinome is indicated.