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  • Author or Editor: W. M. Pedersoli x
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SUMMARY

A single dose of digoxin was injected, iv, into 5 mature male turkeys (0.066 mg/kg of body weight), 8 male ducks (0.066 mg/kg), and 6 roosters (0.33 mg/kg). Twenty-three serial venous blood samples were collected before (baseline) and after the administration of digoxin to turkeys, ducks, and roosters. Plasma concentrations of digoxin were determined in duplicate by a radioimmunoassay that was validated for avian species. The plasma concentrations were best fitted by a 3 (turkeys, ducks)- and 2 (roosters)- compartment open model, with first-order elimination from the central compartment. Significant (P < 0.05) kinetic differences were determined among species. Mean half-life (t½) for ducks, roosters, and turkeys were 8.30 ± 2.70 (mean ± SD), 6.67 ± 3.50, and 23.7 ± 4.8 hours, respectively. The volume of distribution at steady state (Vss) was 14.7 ± 2.9, 3.13 ± 0.49, and 2.27 ± 0.36 L/kg, and total body clearance (cl) of drug was 1.54 ± 0.43, 0.461 ± 0.187, and 0.136 ± 0.022 L/h/kg for ducks, roosters, and turkeys, respectively. The mean residence time was 10.3 ± 3.9, 8.37 ± 4.97, and 16.8 ± 2.2 hours, respectively. Volume of distribution at steady state and cl in ducks were several fold higher than that in turkeys. The terminal half-life of digoxin determined for ducks and roosters in this study was considerably shorter than those previously reported for several mammalian species.

Free access
in American Journal of Veterinary Research

Summary

Twelve mature (5 sexually intact males, 4 castrated males, and 3 females) mixed-breed dogs were surgically thyroidectomized and used in a Latin-square design pharmacokinetic study of orally administered l-thyroxine. The dogs were treated with 44, 22, and 11 μg of l-thyroxine/kg as a single morning dose or in divided doses, morning and evening. Serum concentration of thyroxine (T4) was evaluated to determine a number of pharmacokinetic variables for comparison. Mean steady-state concentrations (Css) were determined from the area under the curve. Variables were analyzed for comparisons between dosages by use of anova.

Concentration at steady state was highest for dogs of the 44-μg/kg of body weight once-daily group and was lowest for dogs of the group given 11 μg/kg in 2 daily doses. Single daily administration resulted in higher Css, except at the 22-μg/kg/d dosage. Clearance was faster for the 22- and 44-μg/kg/d dosages than for the 11-μg/kg/d dosage. The half-life (t1/2) and mean residence time (mrt) also were shorter for the 44-μg/kg/d dosage, possibly indicating more rapid elimination of the drug at higher doses and dose-dependent kinetics. Perhaps, as the dogs’ metabolism increased with higher iodothyronine concentrations, hormone degradation was accelerated. Interval (divided vs single dose) caused some expected changes: maximal concentration was higher and minimal concentration was lower when single administration was used. These undulations resulted in iodothyronine concentrations above the physiologic range for a number of hours, whereas concentration closer to physiologic ranges was achieved by use of divided doses. Delayed absorption (lag time) was seen in 37 of the 72 data sets, but was generally short, about 0.25 hour. Mean time to maximal concentration was 3 to 4 hours. At the higher dosages, serum total T4 concentration was high normal or above normal during most of the time after l-thyroxine administration, but serum concentration of total 3,5,3′-triiodothyronine did not remain within the normal range until the 44-μg/kg/d dosage was used. The customary dosage of 22 μg/kg/d (0.1 mg/10 lb/d) may not be adequate for most dogs. Pharmacokinetic variables appear to be highly dependent on the individual dog. Those with rapid absorption and higher concentration tended to have these characteristics at each dosage in this study. The pharmacokinetic variables, therefore, appear to be highly individualized, and dosages recommended for treatment of hypothyroidism should be considered to be only a starting point for the average dog. To avoid underdosing or overdosing, monitoring of treatment to adjust dose for individual dog kinetic variables seems to be imperative.

Free access
in American Journal of Veterinary Research

Summary

Six healthy mature horses were orally administered a single dose of phenobarbital (26 mg/kg of body weight), then multiple doses (13 mg/kg) orally for 42 consecutive days. Seventeen venous blood samples were collected from each horse after the single dose study and again after the last dose on day 42. Plasma phenobarbital concentration was determined by use of a fluorescence assay validated for horses. Additional blood samples (n = 11) were collected on days 8 and 25 to determine peak and trough concentrations, as well as total body clearance. Phenobarbital disposition followed a one-compartment model. Mean kinetic variables after single and repeated orally administered doses (42 days) were: elimination half-life = 24.2 ± 4.7 and 11.2 ± 2.3 hours, volume of distribution = 0.960 ± 0.060 and 0.914 ± 0.119 L/kg, and clearance = 28.2 ± 5.1 and 57.3 ± 9.6 ml/h/kg, respectively. Results indicated that significant (P < 0.05) difference in half-life and oral clearance existed between single and repeated dosing. The significant decrease in half-life after repeated dosing with phenobarbital may be indicative of enzyme induction. Significant difference was not observed between baseline serum enzyme concentration and concentration measured on day 42, except for γ-glutamyltransferase activity, which was significantly increased on day 42 in 3 of the 6 horses. On the basis of increases in oral clearance observed over 42 days, dose adjustments may be required. By days 25 to 42, pharmacokinetic values indicated that dosages of phenobarbital between 25 and 27 mg/kg administered orally every 24 hours may be needed to maintain steady state plasma concentration of phenobarbital at 20 μg/ml of plasma in mature horses.

Free access
in American Journal of Veterinary Research

SUMMARY

Healthy mature roosters (n = 10) were given gentamicin (5 mg/kg of body weight, IV) and, 30 days later, another dose im Serum concentrations of gentamicin were determined over 60 hours after each drug dosing, using a radioimmunoassay. Using nonlinear least-square regression methods, the combined data of IV and im treatments were best fitted by a 2-compartment open model. The mean distribution phase half-life was 0.203 ± 0.075 hours (mean ± SD) and the terminal half-life was 3.38 ± 0.62 hours. The volume of the central compartment was 0.0993 ± 0.0097 L/kg, volume of distribution at steady state was 0.209 ± 0.013 L/kg, and the total body clearance was 46.5 ± 7.9 ml/h/kg.

Intramuscular absorption was rapid, with a half-life for absorption of 0.281 ± 0.081 hours. The extent of im absorption was 95 ± 18%. Maximal serum concentration of 20.68 ± 2.10 μg/ml was detected at 0.62 ± 0.18 hours after the dose. Kinetic calculations predicted that IM injection of gentamicin at a dosage of 4 mg/kg, q 12 h, and 1.5 mg/kg, q 8 h, would provide average steady-state serum concentrations of 6.82 and 3.83 μg/ml, with minimal steady-state serum concentrations of 1.54 and 1.50 μg/ml and maximal steady-state serum concentrations of 18.34 and 7.70 μg/ml, respectively.

Free access
in American Journal of Veterinary Research