Objective—To determine pharmacokinetics and
excretion of phenytoin in horses.
Animals—6 adult horses.
Procedure—Using a crossover design, phenytoin
was administered (8.8 mg/kg of body weight, IV and
PO) to 6 horses to determine bioavailability (F).
Phenytoin also was administered orally twice daily for
5 days to those same 6 horses to determine steadystate
concentrations and excretion patterns. Blood
and urine samples were collected for analysis.
Results—Mean (± SD) elimination half-life following a
single IV or PO administration was 12.6 ± 2.8 and 13.9
± 6.3 hours, respectively, and was 11.2 ± 4.0 hours following
twice-daily administration for 5 days. Values for
F ranged from 14.5 to 84.7%. Mean peak plasma concentration
(Cmax) following single oral administration
was 1.8 ± 0.68 µg/ml. Steady-state plasma concentrations
following twice-daily administration for 5 days
was 4.0 ± 1.8 µg/ml. Of the 12.0 ± 5.4% of the drug
excreted during the 36-hour collection period, 0.78 ±
0.39% was the parent drug phenytoin, and 11.2 ±
5.3% was 5-(p-hydroxyphenyl)-5-phenylhydantoin (p-HPPH). Following twice-daily administration for 5
days, phenytoin was quantified in plasma and urine
for up to 72 and 96 hours, respectively, and p-HPPH
was quantified in urine for up to 144 hours after
administration. This excretion pattern was not consistent
in all horses.
Conclusion and Clinical Relevance—Variability in F,
terminal elimination-phase half-life, and Cmax following
single or multiple oral administration of phenytoin
was considerable. This variability makes it difficult to
predict plasma concentrations in horses after phenytoin
administration. (Am J Vet Res 2001;62:483–489)
A retrospective study was conducted to establish the prerace venous acid-base and blood gas values of Standardbred horses at rest using big data analytics.
Venous blood samples (73,382) were collected during seven racing seasons from 3 regional tracks in the Commonwealth of Pennsylvania. Horses were detained 2 hours prior to race time.
A mixed-effects linear regression model was used for estimating the marginal model adjusted mean (marginal mean) for all major outcomes. The interaction between age and gender, track, and the interaction between month, treatment (furosemide), and year were the major confounders included in the model. Random effects were set on individual animal nested within trainer. Partial pressure of venous carbon dioxide (PVCO2), partial pressure of oxygen (PVO2), and pH were measured, and base excess (BE), total carbon dioxide (TCO2), and bicarbonate (HCO3−) were calculated.
Significant (P < .001) geographical differences in track locations were seen. Seasonal reductions in acid-base values started in January with significant (P < .001) decreases from adjacent months seen in June, July, and August followed by a gradual return. There were significant increases (P < .001) in BE and TCO2 and decreases in PVO2 with age. Significant differences (P < .001) in acid-base values were seen when comparing genders. A population of trainers were significantly different (P < .001) from the marginal mean and considered outliers.
In a population of horses, big data analytics was used to confirm the effects of geography, season, prerace furosemide, gender, age, and trainer influence on blood gases and the acid-base profile.