Objective—To investigate the pharmacokinetics and behavioral effects of aminorex administered IV and PO in horses.
Procedures—In a cross-over design, aminorex (0.03 mg/kg) was administered IV or PO. Plasma and urinary aminorex concentrations were determined via liquid chromatography– mass spectrometry.
Results—Decrease of aminorex from plasma following IV administration was described by a 3-compartment pharmacokinetic model. Median (range) values of α, β, and γ half-lives were 0.04 (0.01 to 0.28), 2.30 (1.23 to 3.09), and 18.82 (8.13 to 46.64) hours, respectively. Total body and renal clearance, the area under the plasma time curve, and initial volume of distribution were 37.26 (28.61 to 56.24) mL·min/kg, 1.25 (0.85 to 2.05) mL·min/kg, 13.39 (8.82 to 17.37) ng·h/mL, and 1.44 (0.10 to 3.64) L/kg, respectively. Oral administration was described by a 2-compartment model with first-order absorption, elimination from the central compartment, and distribution into peripheral compartments. The absorption half-life was 0.29 (0.12 to 1.07) hours, whereas the β and γ elimination phases were 1.93 (1.01 to 3.17) and 23.57 (15.16 to 47.45) hours, respectively. The area under the curve for PO administration was 10.38 (4.85 to 13.40) ng·h/mL and the fractional absorption was 81.8% (33.8% to 86.9%).
Conclusions and Clinical Relevance—Aminorex administered IV had a large volume of distribution, initial rapid decrease, and an extended terminal elimination. Following PO administration, there was rapid absorption, rapid initial decrease, and an extended terminal elimination. At a dose of 0.03 mg/kg, the only effects detected were transient and central in origin and were observed only following IV administration.
Objective—To compare the pharmacokinetics of
penicillin G and procaine in racehorses following IM
administration of penicillin G procaine (PGP) with
pharmacokinetics following IM administration of penicillin
G potassium and procaine hydrochloride (PH).
Animals—6 healthy adult mares.
Procedure—Horses were treated with PGP (22,000
units of penicillin G/kg of body weight, IM) and with
penicillin G potassium (22,000 U/kg, IM) and PH
(1.55 mg/kg, IM). A minimum of 3 weeks was allowed
to elapse between drug treatments. Plasma and urine
penicillin G and procaine concentrations were measured
by use of high-pressure liquid chromatography.
Results—Median elimination phase half-lives of penicillin
G were 24.7 and 12.9 hours, respectively, after
administration of PGP and penicillin G potassium.
Plasma penicillin G concentration 24 hours after administration
of penicillin G potassium and PH was not significantly
different from concentration 24 hours after
administration of PGP. Median elimination phase halflife
of procaine following administration of PGP (15.6
hours) was significantly longer than value obtained
after administration of penicillin G potassium and PH
Conclusions and Clinical Relevance—Results suggest
that IM administration of penicillin G potassium
will result in plasma penicillin G concentrations for 24
hours after drug administration comparable to those
obtained with administration of PGP. Clearance of procaine
from plasma following administration of penicillin
G potassium and PH was rapid, compared with clearance
following administration of PGP. (Am J Vet Res
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)