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Summary

Serum concentrations of cefotaxime and desacetylcefotaxime were measured in 1-week-old pony foals after iv administration of a single dose of cefotaxime.

The cefotaxime disposition data conformed to a two-compartment model with elimination half-life of 0.60 hour. The combined cefotaxime and desacetylcefotaxime data was best described by a four-compartment model. The apparent half-life describing the disappearance of desacetylcefotaxime was 1.69 hours.

Dosage of 40 mg/kg of body weight given iv every 4 to 6 hours for neonatal foals with gram-negative septicemia and every 2 hours for foals with meningitis is recommended for further study.

Free access
in American Journal of Veterinary Research

Summary

Single doses (2.2 mg/kg of body weight) of phenylbutazone (pbz) were administered iv to 6 neonatal horses (5 to 17 hours old at time of dosing). Plasma concentrations of pbz and its metabolite oxyphenbutazone were monitored serially for 120 hours after drug administration. Pharmacokinetic variables were calculated, using 1- and 2-compartment open models. Descriptive equations from the best model for each foal were then used to derive model-independent variables describing pbz disposition. Median volume of distribution at steady-state was 0.274 L/ kg (range, 0.190 to 0.401 L/kg). Median terminal half-life was 7.4 (6.4 to 22.1) hours, and median total plasma clearance of pbz for foals in this study was 0.018 L/kg/h (range, 0.013 to 0.038 L/kg/h). Volume of distribution was larger, half-life was longer, and total clearance was lower, compared with similar values reported for administration of pbz to adult horses.

Free access
in American Journal of Veterinary Research

Summary

Age, species, and disease state may substantially alter the disposition and clearance of pharmacologic agents. This is particularly important when drugs with low therapeutic index are used in ill neonates. Pharmacokinetic variables for phenylbutazone were determined in 24- to 32-hour-old healthy and endotoxemic calves after iv administration of a single dose (5 mg/kg of body weight, iv). Elimination halflife was 207 and 168 hours, and clearance was 0.708 and 0.828 ml/kg/h in healthy and endotoxemic calves, respectively. Intravenous infusion of endotoxin at the dose (2 μg/kg over 4 hours) given did not significantly alter any of the calculated pharmacokinetic variables. Serum thromboxane B2 concentration was significantly (P = 0.05) suppressed for 3 hours after phenylbutazone administration in healthy calves and for 4 hours in endotoxin-challenged calves. Daily administration of phenylbutazone (10 mg/kg loading, then 5 mg/kg for 9 days) to healthy and endotoxemic calves failed to induce any lesions consistent with nonsteroidal anti-inflammatory drug toxicosis.

Free access
in American Journal of Veterinary Research

Summary

The clinical efficacy of the lazaroid, tirilazad mesylate, a new therapeutic agent for prophylaxis and treatment of endotoxemia, was evaluated in 24 neonatal Holstein calves. Endotoxemia was induced by iv infusion of commercial Escherichia coli lipopolysaccharide (3.25 µg/kg of body weight) over 3 hours. Group-1 calves were given endotoxin alone; group-2 calves were given an infusion of 0.9% sterile saline solution, then were treated with tirilazad mesylate (1.5 mg/kg) 1 hour after the infusion was started. Group-3 calves were treated with tirilazad mesylate 1 hour after the start of the endotoxin infusion, and group-4 calves were given tirilazad mesylate 1 hour before the start of the endotoxin infusion.

Clinical signs of endotoxemia were mitigated by tirilazad mesylate. In addition, tirilazad mesylate protected calves from endotoxin-induced hyperglycemia; treatment after endotoxin infusion decreased the severity of hypoglycemia and prevented lactic acidosis. Treatment with tirilazad mesylate after initiation of endotoxin infusion was as protective as was pretreatment.

Free access
in American Journal of Veterinary Research

SUMMARY

The effect of age on the pharmacokinetics of chloramphenicol was determined after iv administration of chloramphenicol sodium succinate (25 mg/kg of body weight) to 6 foals at 1 day and 3, 7, 14, and 42 days of age. The disposition of chloramphenicol was best described, using a two-compartment open model in all foals at all ages evaluated. Significant age-related changes were observed in values for the major kinetic terms describing the disposition of chloramphenicol in foals; the greatest changes were observed between 1 day and 3 days of age.

The mean ± sd value for elimination rate constant (β) for chloramphenicol in 1-day-old foals (0.131 ± 0.06 h-1) was significantly (P < 0.005) lower than the value in 3-day-old foals (0.514 ± 0.156 h-1), and both values were significantly (P < 0.05) lower than values for β in 7-, 14-, and 42-day-old foals. With increasing age, the increase in the mean value for β resulted in decrease in the harmonic mean elimination half-time (t1/2β) for chloramphenicol, from 5.29 hours in 1-day-old foals to: 1.35 hours in 3-day-old foals; 0.61 hour in 7-day-old foals; 0.51 hour in 14-day-old foals; and 0.34 hour in 42-day-old foals. At 1, 3, and 7 days of age, values for t1/2β of chloramphenicol in a premature foal born after parturition was induced with oxytocin, were considerably longer than comparable t1/2β values for term foals born naturally.

The mean body clearance (ClB) of chloramphenicol in 1-day-old foals (2.25 ± 0.67 ml/min·kg of body weight) was significantly lower than values in: 3-day-old (6.23 ± 2.22 ml/min·kg; P < 0.05); 7-day-old (8.86 ± 1.90 ml/min·kg; P < 0.0005); 14-day-old (9.63 · 1.63 ml/min·kg; P < 0.0005); and 42-day-old (9.68 · 2.76 ml/min·kg; P < 0.0001) foals. In foals of all ages, ClB of chloramphenicol in the parturition-induced premature foal was lower than the mean value for term foals born naturally.

The volume of distribution (V′d[area]) of chloramphenicol decreased progressively with increasing age between day 1 and day 42, so that the mean value for 42-day-old foals (362 ± 163 ml/kg) was less than a third the mean value for 1-day-old foals (1,101 ± 284 ml/kg). The mean value for V′d(area) in 1-day-old foals was significantly greater than values for: 7-day-old (491 ± 158 ml/kg; P < 0.01); 14-day-old (426 ± 65 ml/kg; P < 0.005); and 42-day-old (362 ± 162; P < 0.0005) foals, and the mean value for V′d(area)on day 3 was significantly (P < 0.05) greater than the mean value for V′d(area) on days 7, 14, and 42.

Using dosage calculations based on mean values for the pharmacokinetic terms derived for each age group, it was predicted that to maintain plasma chloramphenicol concentration > 8 μg/ml, chloramphenicol sodium succinate (25 mg/kg) would have to be administered at dose intervals of 10, 3, 1.5, 1.5, and 1 hours in clinically normal foals 1 day and 3, 7, 14, and 42 days, of age, respectively. It was concluded that the marked changes in the disposition of chloramphenicol detectable during the first few days of life, the variation between individuals, the potentially major effect of prematurity, and the potential for compromised liver function in septicemic foals indicate that use of drugs, such as chloramphenicol, which rely heavily on hepatic metabolic processes for elimination, should be avoided whenever possible during the early neonatal period, unless plasma concentration is monitored.

Free access
in American Journal of Veterinary Research

Abstract

Objective

To determine the pharmacokinetics and milk penetration of enrofloxacin (ENR) and ciprofloxacin (CIP) in lactating rabbits and their disposition in suckling rabbits.

Design

Prospective cross-over study.

Animals

6 lactating New Zealand White rabbits and their offspring (16 days after parturition).

Procedure

Serial plasma and milk samples were assayed by use of a high-performance liquid chromatography technique. In vitro protein binding in plasma and skim milk was measured by ultrafiltration. Skim-to-whole milk ratio also was determined. The time course of ENR and CIP was fitted by nonlinear least squares regression analysis, and the pharmacokinetic variables were compared.

Results

The time courses of ENR and CIP in plasma were similar in lactating adult rabbits (mean body clearances, 23.9 and 27.2 ml/min/kg of body weight, for ENR and CIP, respectively). Observed milk-to-plasma ratios (M/P) were determined, using the area under the milk and plasma concentration versus time profiles (ENR, 2.59; CIP, 3.61). Predicted M/P (ENR, 6.35; CIP, 3.04) were calculated from in vitro measurements. Body clearance calculated for ENR and CIP in suckling rabbit pups involved a decrease of 80 and 74%, respectively, over that found in lactating animals.

Conclusions

Observed CIP M/P were correlated to predicted values, which strengthens the argument that CIP passes into the milk by nonionic diffusion. The lack of correlation between observed and predicted ENR M/P pointed out that ENR undergoes faster elimination from milk than that predicted by the diffusional model. Diminished elimination capacity observed in suckling rabbits would result in greater exposure than that predicted from concentrations alone. (Am J Vet Res 1996;57:547–553)

Free access
in American Journal of Veterinary Research

Summary

Age and species reportedly affect the pharmacokinetic variables of nonsteroidal anti-inflammatory drugs. We determined the effect of age on flunixin pharmacokinetic variables in foals during the first month of life. We also estimated the physiologic activity of the drug in neonatal foals by determining the effect of flunixin on thromboxane production during clotting of blood taken from the foals. Flunixin disposition and clearance were determined after iv administration of 1.1 mg of drug/kg of body weight to 5 healthy foals when they were 24 to 28 hours, 10 to 11 days, and 27 to 28 days old. The area under the curve (2,471 μg·min/ml), mean residence time (477 minutes), and zero-time intercept of the elimination phase (4,853 ng/ml) were significantly (P = 0.05) greater, the elimination half-life (339 minutes) and slope of the elimination phase (0.002 L/min) were significantly (P = 0.05) longer, and total body clearance (0.482 ml/min/kg) and zero-time intercept for the distribution phase (2,092 ng/ml) were significantly (P = 0.05) lower at 24 to 28 hours. At each age, a biexponential equation was best fitted to the plasma flunixin concentration from each foal. Thromboxane B2 production during clotting of blood was significantly (P = 0.05) suppressed for 12 hours after flunixin meglumine administration at all ages. Therefore, it appears that although age does alter the disposition and elimination of flunixin in neonatal foals, this effect may be of little consequence because the drug's physiologic activity in foals appears similar to that in mature horses.

Free access
in American Journal of Veterinary Research

Summary

Differences between neonatal and adult animals in their response to drugs can usually be attributed to altered disposition processes. Effect of age on the pharmacokinetics of theophylline was determined after IV administration of the drug to 10 groups of dogs at 1, 2, 3, 4, 8, 12, 16, 24, 52, and 104 weeks of age.

Plasma theophylline concentration curves for all groups were adjusted to a biexponential kinetic, with rapid initial distribution phase and slower elimination phase. It also was noticed that young dogs have a slower elimination half-life (1 week old, t1/2β = 987 minutes) than do older animals (8 weeks old, t1/2β = 138 minutes). The values then plateaued until 16 weeks of age, increasing slightly at more advanced age (104 weeks old, t1/2β = 282 minutes). A similar pattern was followed with respect to clearance (1-week-old pups, Cl = 1.17 ml/min/kg of body weight), which increased progressively to reach a value of 7.09 ml/min/kg at 16 weeks of age, then decreased to 3.5 ml/min/kg at 104 weeks of age. Volume of distribution β, in relation to body weight, was not significantly different between age groups (between 1.2 and 1.6 L/kg; P ≤ 0.03).

Theophylline biotransformation mechanisms may be mainly responsible for Cl and t1/2β variations. This leads us to suggest that quantitative and qualitative modifications in the P-450 mono-oxygenase system are responsible for the variations observed in pharmacokinetic variables of theophylline between dogs of different ages.

These findings may have clinical relevance with regard to the therapeutic range of theophylline. For this reason, dosage should be carefully adjusted in younger animals.

Free access
in American Journal of Veterinary Research

Abstract

Objective

To investigate effects of preterm induction of calving by administration of flumethasone and dinoprost on the lecithin-to-sphingomyelin ratio in amniotic fluid and on neonatal respiratory distress after birth.

Animals

45 dairy cows and their newborn calves.

Procedure

Amniotic fluid from 45 cows was obtained and tested between days 258 and 270 of gestation. Cows were then given flumethasone (10 mg; n = 15), dinoprost (25 mg; n = 15), or saline solution (n = 15). Thirty hours later, left flank cesarean section was performed, amniotic fluid was collected, and the calf was delivered. Blood for determination of progesterone was withdrawn at amniotic fluid sample collections and before induction of calving. Blood for analysis of pH and base deficit was collected from calves during cesarean section and repeatedly after birth. Phospholipids in amniotic fluid were measured by thin-layer chromatography, and progesterone was determined by radioimmunoassay. Base deficit and pH were measured, using a blood gas analyzer.

Results

Before treatments, a corpus luteum was present in all cows and the lecithin-to-sphingomyelin ratio in amniotic fluid did not differ between groups. Thirty hours after injections of flumethasone and dinoprost, progesterone concentration had decreased (P < 0.05) and the lecithin-to-sphingomyelin ratio was significantly (P < 0.05) higher than values in controls. In calves delivered after flumethasone or dinoprost treatments, the degree of acidosis was significantly (P < 0.05) less than that in controls.

Conclusions

Flumethasone and dinoprost, given to pregnant cows, accelerate fetal lung maturation and improve respiratory function after birth. (Am J Vet Res 1997;58:404–407)

Free access
in American Journal of Veterinary Research

cellular constituents. 17 Bovine neutrophils have a high affinity for tulathromycin. 18 In a study 19 of neonatal Holstein calves, the number of circulating neutrophils peaked between birth and 8 hours old and then gradually decreased between peak and

Full access
in American Journal of Veterinary Research