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  • Author or Editor: Jeffrey A. Rudy x
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Abstract

Objective—To investigate the pharmacokinetics and behavioral effects of aminorex administered IV and PO in horses.

Animals—7 Thoroughbreds.

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.

Full access
in American Journal of Veterinary Research

Abstract

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 (1 hour).

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 2000;61:811–815)

Full access
in American Journal of Veterinary Research

Abstract

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)

Full access
in American Journal of Veterinary Research