Effect of intravenous infusion of isotonic sodium bicarbonate solution on acidemic calves with diarrhea

The effect of 1.35% isotonic sodium bicarbonate solution (ISB) administered intravenously on acid-base equilibrium was examined in 18 acidemic Japanese black beef calves with spontaneous diarrhea. The infusion volumes of ISB were decided based on the first half volumes of base needed. In 72.2% (13/18) of calves, improvement of acidemia was detected. There was good correlation (r=0.693, p<0.01) between infused volume of ISB and changes in base excess (y=1.097x + 4.762). Infusion volumes of ISB were 7.5, 10.2, 12.9 and 15.7 ml/kg, respectively, enough to correcting the first half of 5, 10, 15 and 20 mEq/l of base deficit in acidemic calves. Our finding suggested that ISB could be used to correct metabolic acidosis without altering electrolyte concentrations in calves.     

Comparison of the effects of isotonic and hypertonic sodium bicarbonate solutions on acidemic calves experimentally induced by ammonium chloride administration

The objectives of this study were to evaluate and compare the effects of intravenously (IV) administered infusion of isotonic solution (ISB) or hypertonic sodium bicarbonate solution (HSB) on acid-base equilibrium and the plasma osmolarity in acidemic calves experimentally induced by 5 M-NH(4)Cl, IV infusion (1.0 ml/kg, over 1 hr). The ISB and HSB infusion induced progressive and significant increases in their HCO(3)(-) and BE levels that persisted throughout the period of fluid administration. The plasma osmolarity in the ISB groups was significantly decreased. The plasma osmolarity in the HSB group was significantly higher than in the calves in the other groups (p<0.05). ISB solution might be safe and effective for treating and reviving conscious calves from experimentally induced metabolic acidosis.     

Effect of intravenous infusion of a 7.2% hypertonic saline solution on serum electrolytes and osmotic pressure in healthy beagles.

The effect of an intravenous (i.v.) infusion of hypertonic saline solution (HSS; 7.2%, 2,400 mOsmol/kg.H2O) was evaluated by serum electrolyte concentrations and osmotic pressure in the anesthetized beagles. Sixteen beagles were assigned to 3 experimental groups (2.5, 5 or 15 ml/kg of HSS i.v. infusion) or a control group (5 ml/kg of isotonic saline solution (ISS) i.v. infusion) and were monitored for 120 min after the initiation of fluid infusion. The relative plasma volume (rPV) in the 5 ml/kg and 15 ml/kg HSS groups progressively expanded to 143.1 +/- 7.4% at 3 min and 156.4 +/- 5.9% at 5 min after the initiation of the fluid infusion, respectively. Significant increases were not produced by ISS and 2.5 ml/kg HSS infusion. The serum sodium and chloride concentrations in the ISS group were not altered. The 5 ml/kg HSS infusion induced transient high osmotic and sodium levels, and the serum sodium concentration remained under the 160 mM/l after the completion of the HSS infusion. However, the 15 ml/kg HSS infusion induced a constant high osmotic level (340.5-352.8 mOsmol/kg.H2O) and hypernatremia (161.4-174.5 mM/l) from 10 to 90 min after the initiation of the fluid infusion. The 15 ml/kg HSS infusion induced significant decreases in the partial pressure of oxygen (PaO2), reaching 63.7 +/- 8.0 mmHg at 120 min after the initiation of the fluid infusion compared with an immediately before fluid infusion value. On the basis of these findings, 5 ml/kg HSS infusion can be safely administered to healthy beagles for expanding the plasma volume without inducing hypernatremia. A 5 ml/kg HSS infusion is thus recommended for the initial field resuscitation of dogs.     

Hemodynamic and Electrocardiographic Effects of Magnesium Sulfate in Healthy Dogs

We investigated the effects of graded dosages of magnesium given i.v. to anesthetized dogs on blood pressure, cardiac output, and electrophysiology. Magnesium was infused at 0.12 mEq/kg/minute until ventricular fibrillation occurred naturally or was provoked by programmed electrical stimulation or until arrest of the sinuatrial node in 8 dogs. Plasma total magnesium concentrations doubled in 1 minute of that infusion rate, and a hemodynamically safe plasma concentration of 12.2 mEq/L was achieved after 16 minutes of infusion. Heart rate, inotropy, lusitropy, and cardiac output increased up to a cumulative infusion dosage of magnesium of 1.0-2.0 mEq/kg, which produced plasma magnesium concentrations of 8.5-12.2 mEq/L (n = 5). Above the cumulative infusion dosage, inotropy decreased and lusitropy increased until death occurred between cumulative infusion dosages of 5.9 mEq/kg and 10.9 mEq/kg. Arterial pressure and vascular resistance decreased, and PQ interval and QRS complex increased, in a dose-dependent fashion. The relationship between ionized and total magnesium was y = 0.624x - 0.542 (r2 = .986), where y is ionized and x is total magnesium in mEq/L in 3 dogs. In conclusion, a cumulative infusion dosage of 0.1-0.2 mEq/kg of magnesium may be given without changing hemodynamic parameters, but with higher cumulative infusion doses heart rate accelerates. Hemodynamic parameters except those related to blood pressure continued to increase to a cumulative infusion dosage of 2.0 mEq/kg. At higher cumulative infusion dosages dogs became hypotensive and the PQ interval was prolonged. However, dangerous arrhythmias were not provoked until a total dosage of 3.9 mEq/kg.     

Pharmacokinetic disposition and plasma protein binding (in vitro) of chloramphenicol in Bubalus bubalis I*

Eleven buffalo calves (Bubalus bubalis) of 1-1 1/2 years of age and weighing between 64 and 174 kg were given chloramphenicol at the dose rates of 10 and 20 mg/kg body weight. Pharmacokinetic parameters were determined from the plasma levels. The median elimination half-life was estimated to be 2.95 h and the median volumes of distribution were 1.1667 litres/kg with the 10 mg/kg dose and 0.9699 litres/kg with the 20 mg/kg dose. The median metabolic clearance rates were 288.30 and 234.13 ml/h/kg, respectively. From the average plasma concentrations obtained with the 20 mg/kg i.v. dose, it was considered necessary to repeat the drug by the i.m. route with the same dose (four calves) which resulted in prolonging the therapeutic concentration (> 5 μg/ml) until 18 h. At therapeutic concentrations, about 60% of the drug was bound to plasma proteins. Using the overall elimination rate constant (0.2354 h^-1) and the apparent specific volume of distribution (0.97 litres/kg), different dosage regimens were calculated so as to obtain plasma concentrations (C_p min) of 2, 5 and 10 μg/ml.     

The Effects of Equivalent Doses of Tromethamine or Sodium Bicarbonate in Healthy Horses

Objective—To describe the effects of tromethamine, a putative treatment for metabolic acidosis, and to compare its biochemical effects with those of sodium bicarbonate.
Design—Randomized intervention study with repeated measures.
Animals—16 healthy horses, 3 to 17 years old, weighing 391 to 684 kg.
Methods—Ten horses received 3 mEq/kg tromethamine and six received 3 mEq/kg sodium bicarbonate. Samples of venous blood and cerebrospinal fluid (CSF) were collected at intervals before and after drug administration. Heart rate and breathing rate were also recorded at intervals. Results—Median standard base excess increased significantly ( P < .05) from baseline immediately after both bicarbonate and tromethamine. These increases were not significantly different between treatments. Standard base excess returned toward baseline but remained significantly increased 3 hours after infusion of either treatment. After tromethamine, there was a significant decrease in plasma sodium concentration that lasted for at least 90 minutes. After sodium bicarbonate, no change in plasma sodium concentration was detected. Both sodium bicarbonate and tromethamine increased carbon dioxide tension in venous blood and CSF. Despite venous alkalemia, the pH of CSF decreased after both treatments.
Conclusions—Tromethamine and sodium bicarbonate have similar alkalinizing ability. Tromethamine causes hyponatremia, whereas both tromethamine and sodium bicarbonate increase carbon dioxide tension in venous blood and CSF.
Clinical Relevance—If hyponatremia, hypercarbia, and acidosis of the CSF occur after tromethamine is given to horses with existing metabolic acidosis, some of the potential advantages of tromethamine may prove theoretical rather than practical.     

Age-dependent pharmacokinetics of oxytetracycline in ruminants

Oxytetracycline (OTC) was administered intravenously (i.v.) to 3-and 12-week-old calves and lactating cows, and both i.v. and intramuscularly (i.m) to 14-week-old calves and non-lactating cows. Concentrations of OTC were determined in plasma and were analysed kinetically. The pharmacokinetic parameters which were derived using the three-compartment open model were inadequate to describe plasma drug levels in six out of the 23 animals treated i.v., and, therefore, model-independent kinetic parameters were utilized for evaluating age-dependent pharmacokinetics of OTC. In the 3-week-old calves, the total body clearance (Cl b ) was 0.0022 ml/min/kg, the total distribution volume (V d area ) was 2.48 l/kg, and the distribution volume of the central compartment (V 1 ) was 0.56 l/kg. Mean values for Cl b , V d area , and V 1 in 3-week-old calves were two-, three- and four-fold greater, respectively, than the corresponding values in cows. Mean values of Cl b and V d area for the 12-and 14-week-old calves were intermediate between the corresponding values in 3-week-old calves and cows. Dose and state of lactation did not affect the model-independent parameters. The i.v. and i.m. data illustrated that the recommended dose levels of OTC in young calves should be twice those employed in cows for obtaining similar plasma OTC concentration-time profiles.     

Effect of sodium bicarbonate infusions on ionized calcium and total calcium concentrations in serum of clinically normal cats

The effects of sodium bicarbonate (0.5 mEq/kg of body weight, 1.0 mEq/kg, 2.0 mEq/kg, and 4.0 mEq/kg) on ionized and total calcium concentrations were determined in clinically normal cats. Also, serum pH, whole blood pH, and serum albumin, serum total protein, and serum phosphorus concentrations were measured. Intravenous administration of sodium bicarbonate to awake cats decreased serum ionized calcium and serum total calcium concentrations. All dosages of sodium bicarbonate were associated with significant decreases of serum ionized calcium concentration. This effect lasted for greater than 180 minutes when cats were given 2.0 mEq/kg or 4.0 mEq/kg. When cats were given 4 mEq of sodium bicarbonate/kg, serum ionized calcium concentration was significantly decreased, compared with that when cats were given lower doses, but only at 10 minutes after infusion. After sodium bicarbonate infusion, serum total calcium concentration, measured by ion-specific electrode and colorimetry, was lower than baseline values at most of the times evaluated. Decreases in serum ionized calcium and serum total calcium concentrations can be attributed only in part to an increase in serum or whole blood pH and to a decrease in serum protein concentration. Serum total calcium concentrations measured by ion-specific electrode and by colorimetry were positively correlated, but the variability was high. Only 44% of the variability in serum ionized calcium concentration could be predicted when serum total calcium, albumin, total protein, phosphorus, and bicarbonate concentrations and pH were considered.     

Effect of endotoxin on tirilazad mesylate (U74006F) pharmacokinetic parameters in neonatal calves

Rose, M.L., Semrad, S.D., Putnam, M.L., Brown, S.A. Effect of endotoxin on tirilazad mesylate (U74006F) pharmacokinetic parameters in neonatal calves.J. vet. Pharmacol. Therap. 16, 438–445.
The pharmacokinetics of the 21-aminosteroid tirilazad mesylate (U74006F) were studied in both healthy and endotoxin-challenged neonatal calves. Group I calves received a 3-h intravenous (i.v.) infusion of sterile saline (250 ml) and tirilazad mesylate (1.5 mg/kg i.v.) 1 h after the start of the saline infusion. Group II calves received tirilazad mesylate 1 h after the start of a 3-h endotoxin (3.25 g/kg) infusion. The data obtained indicate that tirilazad mesylate follows a biexponential equation in neonatal calves. The area-derived volume of distribution (V_darea) was 9.68 ± 0.759 1/kg in healthy calves and 6.53 ± 1.20 1/kg in endotoxin-challenged calves ( P < 0.05). Similarly, significant (P <0.05) decreases in steady-state volume of distribution (Vj_ss) and central volume (VJ were observed in endotoxin-challenged calves (5.32 ± 0.979 1/kg and 1.68 ± 0.189 1/kg, respectively) compared to healthy calves (7.58 ± 0.834 1/kg and 2.43 ± 0.452 1/kg, respectively). A and B were significantly larger in endotoxin-challenged calves than in healthy calves ( P < 0.05). Rate constants and their associated half-lives, area under the curve and clearance were not significantly altered by endotoxin challenge. Serum thromboxane generation (ex vivo) was evaluated as a marker of the drug's physiologic activity. There was no significant difference in thromboxane generation during clotting of blood from healthy and endotoxemic calves treated with tirilazad mesylate.     

Effect of parenteral administration of glutamine on autophagy of liver cell and immune responses in weaned calves

The objectives of this study were to determine the effects of an increased jugular supply of L‐Gln on post‐weaning growth, immune responses, intestinal morphology and autophagy of weaned calves. At 35 days of age, 24 Holstein calves (initial 50 ± 1.5 kg; 35 ± 2 day of age) were randomly allocated to four treatments, and each treatment included five male and one female calves. Holstein calves were assigned to treatments of (i) i.v. infusion of 2 l of 0.85% NaCl, Control group [C]; (ii) i.v. infusion of 8 g/day of L‐Gln mixed with 2 l of 0.85% NaCl solution [L]; (iii) i.v. infusion of 16 g/day of L‐Gln mixed with 2 l of 0.85% NaCl solution [M]; and (iv) i.v. infusion of 32 g/day of L‐Gln mixed with 2 l of 0.85% NaCl [H]; The infusion was 2 h/day for each of 14 consecutive days starting on day 1 after weaning. Feed and water were freely available to all calves. All calves were killed on the 14th day post‐weaning for measurements of autophagy of liver cell and intestinal morphology. Gln has no effect on dry matter intake (DMI) and average daily gain (ADG). Gln infusion increased quadratically the abundance of CD4+, monocyte and the ratio of CD4+/CD8+. The urea N, Gln and Glucose in plasma increased linearly with increasing Gln loads. Gln infusion increased quadratically villus height and crypt depth of intestine. The autophagy level of liver cell was improved with the Gln infusion dose increased.     

Comparative disposition kinetics and plasma protein binding of gentamicin sulphate in three juvenile animal species

The pharmacokinetics of gentamicin was studied in lambs, calves and foals, respectively after single intravenous (i.v.) injections of 5 mg kg(-1) body weight. The plasma concentration-time curves of gentamicin sulphate were best fitted to follow a two-compartment open model in calves and foals and a three-compartment open model in lambs. Gentamicin showed high plasma level at 5 min post-injection. Then its concentration decreased gradually until its minimum detectable level at 10 and 12 h post-injection in foals and calves, respectively, was reached. In contrast, the plasma concentrations were much higher in lambs and persisted up to 48 h from the onset of injection. Values of pharmacokinetic parameters for gentamicin sulphate in different animals after i.v. injections were calculated. Pharmacokinetic data in lambs demonstrated a triphasic decline in plasma gentamicin concentration with slow terminal elimination phase (washout phase) with (t(1/2y)) of 7.7 h. Gentamicin showed a small volume of distribution Vd(ss) (80.3 ml kg(-1)) in lambs indicating that the drug is slightly distributed in extra-vascular tissues. The overall rate of total body clearance ClB in lambs was (0.46 ml kg(-1)) slower than in calves (1.5 ml kg(-1)) and foals (2.7 ml kg(-1)). In vitro protein binding per cent of gentamicin sulphate in plasma were 16.80, 11.03 and 7.98% in lambs, calves and foals. The results of this study emphasize the importance of determining the pharmacokinetics of gentamicin in each species of young animals separately.     

Effect of sodium bicarbonate infusion on serum osmolality, electrolyte concentrations, and blood gas tensions in cats.

The effects of single IV injections of sodium bicarbonate (0.5 mEq/kg of body weight, 1 mEq/kg, 2 mEq/kg, and 4 mEq/kg) on serum osmolality, serum sodium, chloride, and potassium concentrations, and venous blood gas tensions in 6 healthy cats were monitored for 180 minutes. Serum osmolality increased and remained significantly (P less than 0.05) increased for 120 minutes in cats given 4 mEq of sodium bicarbonate/kg. Serum sodium was increased significantly (P less than 0.05) for 30 minutes in cats given 4 mEq of sodium bicarbonate/kg. Serum sodium decreased and remained significantly (P less than 0.05) decreased for 120 minutes in cats given 1 g of 20% mannitol/kg, and serum osmolality was significantly (P less than 0.05) decreased at 30 and 60 minutes. Serum chloride decreased significantly (P less than 0.05) for 10 minutes in cats given 1 mEq of sodium bicarbonate/kg, and was significantly decreased for 30 minutes in cats given 2 mEq and 4 mEq of sodium bicarbonate/kg. Serum chloride decreased and remained significantly (P less than 0.05) decreased for 30 minutes in cats given 1 g of 20% mannitol/kg. Serum sodium and serum osmolality did not change significantly (P less than 0.05) in cats given 4 ml of 0.9% sodium chloride/kg. Serum potassium decreased significantly (P less than 0.05) for 10 minutes in cats given 1 mEq of sodium bicarbonate/kg, and for 120 minutes in cats given 2 mEq/kg or 4 mEq/kg. There was a significantly (P less than 0.05) greater decrease in serum potassium that lasted for 30 minutes after given sodium bicarbonate at the dosage of 4 mEq/kg, compared with other dosages given.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of intravenous hyperosmotic sodium bicarbonate on arterial and cerebrospinal fluid acid-base status and cardiovascular function in calves with experimentally induced respiratory and strong ion acidosis

The objectives of this study were to determine the effects of hyperosmotic sodium bicarbonate (HSB) administration on arterial and cerebrospinal fluid (CSF) acid-base balance and cardiovascular function in calves with experimentally induced respiratory and strong ion (metabolic) acidosis. Ten healthy male Holstein calves (30-47 kg body weight) were instrumented under halothane anesthesia to permit cardiovascular monitoring and collection of blood samples and CSE Respiratory acidosis was induced by allowing the calves to spontaneously ventilate, and strong ion acidosis was subsequently induced by i.v. administration of L-lactic acid. Calves were then randomly assigned to receive either HSB (8.4% NaHCO3; 5 ml/kg over 5 minutes, i.v.; n=5) or no treatment (controls, n=5) and monitored for 1 hour. Mixed respiratory and strong ion acidosis was accompanied by increased heart rate, cardiac index, mean arterial pressure, cardiac contractility (maximal rate of change of left ventricular pressure), and mean pulmonary artery pressure. Rapid administration of HSB immediately corrected the strong ion acidosis, transiently increased arterial partial pressure of carbon dioxide (P(CO2)), and expanded the plasma volume. The transient increase in arterial P(CO2) did not alter CSF P(CO2) or induce paradoxical CSF acidosis. Compared to untreated control calves, HSB-treated calves had higher cardiac index and contractility and a faster rate of left ventricular relaxation for 1 hour after treatment, indicating that HSB administration improved myocardial systolic function. We conclude that rapid i.v. administration of HSB provided an effective and safe method for treating strong ion acidosis in normovolemic halothane-anesthetized calves with experimentally induced respiratory and strong ion acidosis. Fear of inducing paradoxical CSF acidosis is not a valid reason for withholding HSB administration in calves with mixed respiratory and strong ion acidosis.     

Investigations on the association of D-lactate blood concentrations with the outcome of therapy of acidosis, and with posture and demeanour in young calves with diarrhoea

The objective of this prospective study was to elucidate whether amounts of bicarbonate needed for correction of acidosis and normalization of clinical signs are influenced by blood D-lactate concentrations in calves with diarrhoea. In 73 calves up to 3 weeks old with acute diarrhoea and base excess values below -10 mmol/l correction of acidosis was carried out within 3.5-h by intravenous administration of an amount of sodium bicarbonate which was calculated using the formula: HCO (mmol) = body mass (kg) x base deficit (mmol/l) x 0.6 (l/kg). Clinical signs, venous base excess, and plasma D-lactate concentrations were monitored immediately following admission, following correction of acidosis at 4 h and 24 h after admission. The base excess and plasma D-lactate concentrations throughout the study were -17.8 +/- 4.0, -0.4 +/- 0.4, -3.0 +/- 5.5 mmol/l (base excess), and 10.0 +/- 4.9, 9.8 +/- 4.8, 5.4 +/- 3.4 mmol/l (D-lactate) for the three times of examination. Metabolic acidosis was not corrected in more than half of the calves (n = 43) by the calculated amount of bicarbonate, whereas the risk of failure to correct acidosis increases with D-lactate concentrations. The study shows that calves with elevated D-lactate concentrations do not need additional specific therapy, as D-lactate concentrations regularly fall following correction of acidosis and restitution of body fluid volume, for reasons that remain unclear. However, calves with distinct changes in posture and demeanour need higher doses of bicarbonate than calculated with the factor of 0.6 in the formula mentioned above probably because of D-hyperlactataemia.     

Effects of a hypertonic saline solution and dextran 70 combination in the treatment of diarrhoeic dehydrated calves

Thirty dehydrated diarrheic calves aged 2-45 days were used to study the effects of small volume intravenous 7.2% hypertonic saline and 6% dextran 70 solution in combination with alkalinising oral fluids and to compare this therapy with the large volume intravenous isotonic saline with alkalinising oral fluid treatment. This study included a total of 30 diarrhoeic dehydrated calves aged 2-45 days. After routine clinical and haematological examinations, the calves were allotted to two treatment groups. Isotonic saline solution (32 ml/kg, i.v.) with an oral electrolyte solution (22 ml/kg, p.o.) were administered to group I (control), and the combination of 7.2% hypertonic saline in 6% dextran 70 solutions (HSD) (4 ml/kg, i.v.) with an oral electrolyte solution (50 ml/kg, p.o.) were administered to group II (test). Additionally, an oral electrolyte solution (50 ml/kg, p.o.) was readministered to both groups at 12 h of the study. The clinical and haematological examinations of all calves were performed both before and after the treatment at the 1/2, 1, 2, 4, 12 and 24 h. The capillary refill time, peripheral pulse quality, dehydration degrees, mental status, haematocrit rates, haemoglobin and plasma values after treatment were found to be statistically different compared with the values before treatment. In comparison with group I, group II is observed to have shorter capillary refill time at 1, 4 and 12 h (P < 0.001) and better peripheral pulse quality at 1/2 (P < 0.05), 1, 2, 4 and 12 h (P < 0.001). Moreover, the degree of dehydration in group II, was significantly improved at 2 (P < 0.01), 4 and 12 h. Results of the study indicated that administration of low volumes of hypertonic sodium chloride and dextran 70 solution combinations with oral electrolyte solutions was concluded as quicker, practical, economical and most importantly an effective way for the treatment of dehydrated diarrhoeic calves.     

Endotoxin-induced changes in the hemostatic system in neonatal calves: the effect of antiserum to a mutant Escherichia coli (J-5)

Changes in the hemostatic system were studied in 22 neonatal calves given a small dosage of Escherichia coli endotoxin (0.5 microgram/kg) by slow (5-hour) IV infusion. The effect of pretreatment with an antiserum to mutant of E coli O111:B4 (J-5) was evaluated. The platelet count, plasma fibrinogen concentration, prothrombin time, and activated partial thromboplastin time changed significantly from base line during and after endotoxin infusions in all calves. The mean platelet count was significantly decreased from 1 through 24 hours after endotoxin infusion was started. Mean plasma fibrinogen was decreased 2 through 12 hours after endotoxin infusion was started. The mean prothrombin time and activated partial thromboplastin time were significantly greater than base line at 3 to 6 hours and 3 to 12 hours, respectively, after endotoxin infusion was started. Serum concentration of fibrinolytic degradation products remained less than 10 micrograms/ml. Bovine J-5 antiserum did not prevent the endotoxin-induced changes in the hemostatic system of these neonatal calves.     

High performance liquid chromatography and pharmacokinetics of the non-steroidal anti-inflammatory drug oxindanac in calves

A high-performance liquid chromatographic method for the determination of the non-steroidal anti-inflammatory drug, oxindanac, in calf plasma is described. Recoveries over the concentration range 0.3 75 to 62.5 μg/ml were 90.2–107.8% with interassay coefficients of variation of 2.1–22.3%. The limit of detection was estimated as 0.10 μg/ml and the limit of quantification calculated to be 0.24 pg/ml in a 1 ml plasma sample. This method was used to establish the pharmacokinetics following intravenous (i.v.), intramuscular (i.m.) and oral (p.o.) administration to calves of oxindanac at a dose rate of 2 mg/kg. The elimination t ¹/₂, was long ( t 1/2 21.2 h after i.v. injection) and absorption was rapid (t¹/_2B 0.072 h) and complete ( F > 100%) following i.m. administration. Bioavailability was incomplete ( F = 66.6%) following p.o. administration to calves that had been fed on milk, and Wagner-Nelson analysis revealed twoabsorption phases ( t ¹/₂'s 0.20 and 1.9 h). Oxindanac produced long-lasting inhibition of serum TxB₂ production, with mean k_max values (% inhibition) of 96.8, 94.1 and 81.3 following i.v., i.m. and p.0. administration, respectively. A single i.v. or i.m. injection of 2 mg/kg oxindanac will probably be active in calves for at least 36–48 h.     

Clinical evaluation of sodium bicarbonate, sodium L-lactate, and sodium acetate for the treatment of acidosis in diarrheic calves

Thirty-six dehydrated diarrheic neonatal calves were used to study the effects of various alkalinizing compounds on acid-base status, the changes in central venous pressure (CVP) in response to rapid IV infusion of large volumes of fluid, and the correlation of acid-base (base deficit) status, using a depression scoring system with physical determinants related to cardiovascular and neurologic function. Calves were allotted randomly to 4 groups (9 calves/group). Over a 4-hour period, each calf was given two 3.6-L volumes (the first 3.6 L given in the first hour) of a polyionic fluid alone (control group) or were given the polyionic fluid with sodium bicarbonate, sodium L-lactate, or sodium acetate added (50 mmol/L). Acid-base status, hematologic examination, and biochemical evaluations were made immediately before infusion of each fluid (at entry) and after 3.6, 4.8, and 7.2 L of fluid had been given. Compared with control values, bicarbonate, lactate, and acetate had significantly greater alkalinizing effects on pH (P less than 0.01) and base deficit (P less than 0.01) after 3.6, 4.8, and 7.2 L of fluid were given. Bicarbonate had the most rapid alkalinizing effect and induced greater changes in base deficit (P less than 0.01) than did acetate or lactate at each of the 3 administered fluid volumes evaluated. Acetate and lactate had similar alkalinizing effects on blood. Rehydration alone did not improve acid-base status. The CVP was elevated in 10 (28%) of the 36 calves after 1 hour of fluid (3.6 L) administration, but significant differences in body weight, PCV, and clinical condition or depression score at entry were not found between calves with elevated CVP and those with normal CVP.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparative pharmacokinetics of marbofloxacin in healthy and Mannheimia haemolytica infected calves

The pharmacokinetics of marbofloxacin were investigated in healthy (n=8) and Mannheimia haemolytica naturally infected (n=8) Simmental ruminant calves following intravenous (i.v.) and intramuscular (i.m.) administration of 2 mg kg(-1) body weight. The concentration of marbofloxacin in plasma was measured using high performance liquid chromatography with ultraviolet detection. Following i.v. administration of the drug, the elimination half-life (t(1/2 beta)) and mean residence time (MRT) were significantly longer in diseased calves (8.2h; 11.13 h) than in healthy ones (4.6 h; 6.1 h), respectively. The value of total body clearance (CL(B)) was larger in healthy calves (3 ml min(-1) kg(-1)) than in diseased ones (1.3 ml min(-1) kg(-1)). After single intramuscular (i.m.) administration of the drug, the elimination half-life, mean residence time (MRT) and maximum plasma concentration (C(max)) were higher in diseased calves (8.0, 12 h, 2.32 microg ml(-1)) than in healthy ones (4.7, 7.4 h, 1.4 microg ml(-1)), respectively. The plasma concentrations and AUC following administration of the drug by both routes were significantly higher in diseased calves than in healthy ones. Protein binding of Marbofloxacin was not significantly different in healthy and diseased calves. The mean value for MIC of marbofloxacin for M. haemolytica was 0.1+/-0.06 microg ml(-1). The C(max)/MIC and AUC(24)/MIC ratios were significantly higher in diseased calves (13.0-64.4 and 125-618 h) than in healthy calves (8-38.33 and 66.34-328 h). The obtained results for surrogate markers of antimicrobial activity (C(max)/MIC, AUC/MIC and T > or = MIC) indicate the excellent pharmacodynamic characteristics of the drug in diseased calves with M. haemolytica, which can be expected to optimize the clinical efficacy and minimize the development of resistance.     

Probenecid effect on cefuroxime pharmacokinetics in calves

Cefuroxime pharmacokinetics were studied in unweaned calves. The antibiotic was administered at 10 mg/kg to six calves i.v., to 12 calves i.m. and to ten of the previous 12 calves i.m. at 10 mg/kg together with probenecid at 40 mg/kg. Intramuscular doses of cefuroxime alone at 20 mg/kg were given to seven calves; to five of these calves cefuroxime was also given together with probenecid at 40 mg/kg and at 80 mg/kg. The serum concentration-time data were analyzed using statistical moment theory (SMT). The elimination half-life (t1/2) was 69.2 min (harmonic mean) after i.v. and 64.8 min and 64.9 min following i.m. administration of the lower and higher dose, respectively. Co-administration of probenecid did not affect the t1/2. The mean residence time (MRT) was 80.9 +/- 23.5 min (mean +/- SD) after i.v. and 117.8 +/- 9.3 min and 117.7 +/- 5.4 min after i.m. administration of cefuroxime at 10 and 20 mg/kg, respectively. The MRTi.m. following administration of cefuroxime at 10 mg/kg together with probenecid at 40 mg/kg was 140.0 +/- 8.8 min. The MRTi.m. values were 132.8 +/- 2.3 min and 150.8 +/- 5.1 min after cefuroxime was given at 20 mg/kg together with probenecid at 40 mg/kg or 80 mg/kg, respectively. The total body clearance (ClT) was 3.56 +/- 1.11 ml/min/kg and the volume of distribution at steady state (Vd(ss] 0.270 +/- 0.051 l/kg. The MIC90 values of cefuroxime were 16 micrograms/ml for E. coli and Salmonella isolates, 0.5 microgram/ml for Pasteurella multocida and 2.0 micrograms/ml for P. haemolytica.