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veterinary medicine; however, the lack of pharmacokinetic data in turtles often makes it challenging to evaluate potential clinical efficacy despite the availability of sensitivity results. 5 , 6 Ceftazidime, a third-generation cephalosporin, is often used

Open access
in American Journal of Veterinary Research

administration to veal calves are limited. Furthermore, marked differences in drug pharmacokinetics have been observed between young and adult animals. 11 Differences in drug distribution and elimination in young food-producing animals are of particular concern

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in American Journal of Veterinary Research

–3 Marbofloxacin has the highest activity of the veterinary fluoroquinolones against P aeruginosa . 2 The drug is well absorbed after oral administration and has a wide safety margin with few adverse effects in dogs. 3,4 Marbofloxacin pharmacokinetics have been

Full access
in Journal of the American Veterinary Medical Association

food or large amounts of tablets 20 ). The purpose of the study reported here was to investigate the effects of oral administration of AC and urine alkalinization (via oral administration of sodium bicarbonate) on the pharmacokinetics of carprofen

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in American Journal of Veterinary Research

. Investigators of several studies 9–18 have reported alterations in plasma pharmacokinetics of drugs in diseased animals, compared with results for their healthy counterparts. Investigators of a recent study 7 found a correlation between low milk production and

Full access
in Journal of the American Veterinary Medical Association

Abstract

Objective—To investigate the feasibility of using multivariate cluster analysis to meta-analyze pharmacokinetic data obtained from studies of pharmacokinetics of ampicillin trihydrate in cattle and identify factors that could account for variability in pharmacokinetic parameters among studies.

Sample Population—Data from original studies of the pharmacokinetics of ampicillin trihydrate in cattle in the database of the Food Animal Residue Avoidance Databank.

Procedure—Mean plasma or serum ampicillin concentration versus time data and potential factors that may have affected the pharmacokinetics of ampicillin trihydrate were obtained from each study. Noncompartmental pharmacokinetic analyses were performed, and values of pharmacokinetic parameters were clustered by use of multivariate cluster analysis. Practical importance of the clusters was evaluated by comparing the frequency of factors that may have affected the pharmacokinetics of ampicillin trihydrate among clusters.

Results—A single cluster with lower mean values for clearance and volume of distribution of ampicillin trihydrate administered PO, compared with other clusters, was identified. This cluster included studies that used preruminant calves in which feeding was withheld overnight and calves to which probenecid had been administered concurrently.

Conclusions and Clinical Relevance—Meta-analysis was successful in detecting a potential subpopulation of cattle for which factors that explained differences in pharmacokinetic parameters could be identified. Accurate estimates of pharmacokinetic parameters are important for the calculation of dosages and extended withdrawal intervals after extralabel drug administration. (Am J Vet Res 2005;66:108–112)

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in American Journal of Veterinary Research

and pyrexia. 2 , 6 , 7 Only a few reports on acetaminophen (APAP) pharmacokinetics in poultry are present in the literature. Its pharmacokinetics were reported following a single oral dose of 10 mg/kg to chickens and turkeys and after an IP injection

Full access
in Journal of the American Veterinary Medical Association

SUMMARY

Plasma pharmacokinetic variables of benazeprilat, the active metabolite of the angiotensin-converting enzyme (ace) inhibitor benazepril, were evaluated in healthy Beagles. Benazeprilat was administered iv at a dosage of 0.5 mg/kg of body weight (n = 9). The elimination half-life of benazeprilat was 3.5 hours, although an additional terminal phase was observed in some dogs. Vehicle (gelatin capsules) or benazepril at dosages of 0.125, 0.25, 0.5, or 1.0 mg/kg was administered orally as a single administration, then once daily for 15 consecutive days (n = 5 or 6/group). Peak benazeprilat concentrations were rapidly attained by 2 hours. Benazeprilat concentrations accumulated moderately with repeated administration, with a peak concentration that was 23% higher and an area under the concentration-time curve that was 34% higher after the 15th dose of benazepril, compared with values after a single dose. The effective half-life for accumulation for all 4 dosages was 12 hours. Steady-state concentrations at 2 hours after administration were achieved after a median (range) of 1 (1 to 6) dose(s).

Pharmacodynamic variables were assessed by measurement of plasma ace activity after oral administration of benazepril or vehicle. All dosages of benazepril caused profound inhibition of ace, with rapid onset of activity (time to peak effect, 2 hours) and long duration of action (single administration of all 4 doses induced inhibition of ace that was significantly different from the value in the control [vehicle-treated] dogs for all time points between 1 and 30 hours). Maximal inhibition at all time points was induced by the 0.25- mg/kg dosage at a single administration and with the lowest dosage tested (0.125 mg/kg) at steady state. At steady state, the 0.25-mg/kg dosage caused (mean ± sem) 96.9 ± 2.0% inhibition of ace activity at maximal effect and 83.6 ± 4.2% at trough effect (24 hours after dosing), indicating minimal variation in peak/trough effect. Steady-state inhibition of ace activity at both peak and trough drug effect was achieved after 1 to 4 doses. The data indicate that benazepril is a potent and long-acting ace inhibitor in dogs.

Free access
in American Journal of Veterinary Research

Abstract

Objective—To develop a flow-limited, physiologicbased pharmacokinetic model for use in estimating concentrations of sulfamethazine after IV administration to swine.

Sample Population—4 published studies provided physiologic values for organ weights, blood flows, clearance, and tissue-to-blood partition coefficients, and 3 published studies provided data on plasma and other tissue compartments for model validation.

Procedure—For the parent compound, the model included compartments for blood, adipose, muscle, liver, and kidney tissue with an extra compartment representing the remaining carcass. Compartments for the N-acetyl metabolite included the liver and the remaining body. The model was created and optimized by use of computer software. Sensitivity analysis was completed to evaluate the importance of each constant on the whole model. The model was validated and used to estimate a withhold interval after an IV injection at a dose of 50 mg/kg. The withhold interval was compared to the interval estimated by the Food Animal Residue Avoidance Databank (FARAD).

Results—Specific tissue correlations for plasma, adipose, muscle, kidney, and liver tissue compartments were 0.93, 0.86, 0.99, 0.94, and 0.98, respectively. The model typically overpredicted concentrations at early time points but had excellent accuracy at later time points. The withhold interval estimated by use of the model was 120 hours, compared with 100 hours estimated by FARAD.

Conclusions and Clinical Relevance—Use of this model enabled accurate prediction of sulfamethazine pharmacokinetics in swine and has applications for food safety and prediction of drug residues in edible tissues. (Am J Vet Res 2005;66:1686–1693)

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in American Journal of Veterinary Research

toxic effects in several species. 9 Although gabapentin has been used increasingly in cats, the authors are not aware of any published data on the pharmacokinetics of this drug in this species. Without such data, it is difficult to make rational dosing

Full access
in American Journal of Veterinary Research