Objective—To determine the effects that routine histologic
processing has on the dimensions of samples
of normal skin of dogs and assess whether the inclusion
of a muscle or fascial layer in such samples alters
Sample Population—Skin samples obtained from 6
medium-sized adult dogs with grossly normal skin.
Procedure—From each dog, skin samples (with or
without underlying fascia or muscle) were obtained
from 3 sites bilaterally (6 samples/dog) and processed
routinely for histologic evaluation; their dimensions
were measured at intervals during the experiment.
Results—As a result of processing, skin samples
decreased in size (combined percentage change in
length and width) and increased in thickness, compared
with their original dimensions. Samples without
fascia or muscle decreased in size by 21.1% to 32.0%
and increased in thickness by 45.1% to 75.8%. The
site of sample origin influenced processing-associated
changes in sample size but did not affect the
change in thickness. Decreases in dimensions did not
vary with inclusion of fascia but did vary with inclusion
of muscle. The change in thickness did not vary
with inclusion of a layer of fascia or muscle.
Conclusions and Clinical Relevance—Processing of
skin samples obtained from dogs for histologic evaluation
can cause changes in sample dimensions; samples
may decrease in length and width by as much as
32% and increase in thickness by 75.8%, compared
with their original dimensions. The presence of muscle
in canine skin samples can restrict the amount of
shrinkage in length or width associated with processing.
(Am J Vet Res 2005;66:500–505)
OBJECTIVE To determine the effect of age on the pharmacokinetics and pharmacodynamics of flunixin meglumine following IV and transdermal administration to calves.
ANIMALS 8 healthy weaned Holstein bull calves.
PROCEDURES At 2 months of age, all calves received an injectable solution of flunixin (2.2 mg/kg, IV); then, after a 10-day washout period, calves received a topical formulation of flunixin (3.33 mg/kg, transdermally). Blood samples were collected at predetermined times before and for 48 and 72 hours, respectively, after IV and transdermal administration. At 8 months of age, the experimental protocol was repeated except calves received flunixin by the transdermal route first. Plasma flunixin concentrations were determined by liquid chromatography-tandem mass spectroscopy. For each administration route, pharmacokinetic parameters were determined by noncompartmental methods and compared between the 2 ages. Plasma prostaglandin (PG) E2 concentration was determined with an ELISA. The effect of age on the percentage change in PGE2 concentration was assessed with repeated-measures analysis. The half maximal inhibitory concentration of flunixin on PGE2 concentration was determined by nonlinear regression.
RESULTS Following IV administration, the mean half-life, area under the plasma concentration-time curve, and residence time were lower and the mean clearance was higher for calves at 8 months of age than at 2 months of age. Following transdermal administration, the mean maximum plasma drug concentration was lower and the mean absorption time and residence time were higher for calves at 8 months of age than at 2 months of age. The half maximal inhibitory concentration of flunixin on PGE2 concentration at 8 months of age was significantly higher than at 2 months of age. Age was not associated with the percentage change in PGE2 concentration following IV or transdermal flunixin administration.
CONCLUSIONS AND CLINICAL RELEVANCE In calves, the clearance of flunixin at 2 months of age was slower than that at 8 months of age following IV administration. Flunixin administration to calves may require age-related adjustments to the dose and dosing interval and an extended withdrawal interval.