OBJECTIVE To determine the pharmacokinetics of voriconazole administered PO with or without food to red-tailed hawks (Buteo jamaicensus) and whether any observed variability could be explained by measured covariates to inform dose adjustments.
ANIMALS 7 adult red-tailed hawks.
PROCEDURES In a crossover study design, hawks were randomly assigned to first receive voriconazole (15 mg/kg, PO) injected into a dead mouse (n = 3; fed birds) or without food (4; unfed birds). Sixteen days later, treatments were reversed. Blood samples were collected at various points to measure plasma voriconazole concentrations by ultraperformance liquid chromatography. Pharmacokinetic data were analyzed by noncompartmental methods and fit to a compartmental model through nonlinear mixed-effects regression, with feeding status and body weight investigated as covariates.
RESULTS Voriconazole was well absorbed, with quantifiable plasma concentrations up to 24 hours after administration. Mean plasma half-life was approximately 2 hours in fed and unfed birds. Administration of the voriconazole in food delayed absorption, resulting in a significant delay in time to maximum plasma concentration. The final compartmental model included a categorical covariate to account for this lag in absorption as well as body weight as a covariate of total body clearance (relative to unknown bioavailability).
CONCLUSIONS AND CLINICAL RELEVANCE A single dose of voriconazole (15 mg/kg) administered PO to red-tailed hawks resulted in mean plasma voriconazole concentrations greater than the targeted value (1 μg/mL). Additional studies with larger sample sizes and multidose regimens are required before the model developed here can be applied in clinical settings.
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
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)
Objective—To determine the pharmacokinetic parameters of xylazine, ketamine, and butorphanol (XKB) administered IM and sodium salicylate (SAL) administered PO to calves and to compare drug effects on biomarkers of pain and distress following sham and actual castration and dehorning.
Animals—40 Holstein bull calves from 3 farms.
Procedures—Calves weighing 108 to 235 kg (n = 10 calves/group) received one of the following treatments prior to sham (period 1) and actual (period 2) castration and dehorning: saline (0.9% NaCl) solution IM (placebo); SAL administered PO through drinking water at concentrations from 2.5 to 5 mg/mL from 24 hours prior to period 1 to 48 hours after period 2; butorphanol (0.025 mg/kg), xylazine (0.05 mg/kg), and ketamine (0.1 mg/kg) coadministered IM immediately prior to both periods; and a combination of SAL and XKB (SAL+XKB). Plasma drug concentrations, average daily gain (ADG), chute exit velocity, serum cortisol concentrations, and electrodermal activity were evaluated.
Results—ADG (days 0 to 13) was significantly greater in the SAL and SAL+XKB groups than in the other 2 groups. Calves receiving XKB had reduced chute exit velocity in both periods. Serum cortisol concentrations increased in all groups from period 1 to period 2. However, XKB attenuated the cortisol response for the first hour after castration and dehorning and oral SAL administration reduced the response from 1 to 6 hours. Administration of XKB decreased electrodermal activity scores in both periods.
Conclusions and Clinical Relevance—SAL administered PO through drinking water decreased cortisol concentrations and reduced the decrease in ADG associated with castration and dehorning in calves.
Objective—To determine the elimination kinetics of
ceftiofur hydrochloride in milk after intramammary
administration in lactating dairy cows.
Animals—5 lactating dairy cows.
Procedure—After collection of baseline milk samples,
300 mg (6 mL) of ceftiofur was infused into the
left front and right rear mammary gland quarters of
each cow. Approximately 12 hours later, an additional
300 mg of ceftiofur was administered into the
same mammary gland quarters after milking. Milk
samples were collected from each mammary gland
quarter every 12 hours for 10 days. Concentrations of
ceftiofur and its metabolites in each milk sample
were determined to assess the rate of ceftiofur elimination.
Results—Although there were considerable variations
among mammary gland quarters and individual
cows, ceftiofur concentrations in milk from all treated
mammary gland quarters were less than the tolerance
(0.1 µg/mL) set by the FDA by 168 hours (7 days)
after the last intramammary administration of ceftiofur.
No drug concentrations were detected in milk
samples beyond this period. Ceftiofur was not detected
in any milk samples from nontreated mammary
gland quarters throughout the study.
Conclusions and Clinical Relevance—Ceftiofur
administered by the intramammary route as an extralabel
treatment for mastitis in dairy cows reaches
concentrations in milk greater than the tolerance set
by the FDA. Results indicated that milk from treated
mammary gland quarters should be discarded for a
minimum of 7 days after intramammary administration
of ceftiofur. Elimination of ceftiofur may be correlated
with milk production, and cows producing smaller
volumes of milk may have prolonged withdrawal
times. (J Am Vet Med Assoc 2004;224:1827–1830)