Pharmacokinetics, pharmacodynamics, and metabolism of acepromazine following intravenous, oral, and sublingual administration to exercised Thoroughbred horses

Abstract

Acepromazine is a tranquilizer used commonly in equine medicine. This study describes serum and urine concentrations and the pharmacokinetics and pharmacodynamics of acepromazine following intravenous, oral, and sublingual (SL) administration. Fifteen exercised adult Thoroughbred horses received a single intravenous, oral, and SL dose of 0.09 mg/kg of acepromazine. Blood and urine samples were collected at time 0 and at various times for up to 72 hr and analyzed for acepromazine and its two major metabolites (2-(1-hydroxyethyl) promazine and 2-(1-hydroxyethyl) promazine sulfoxide) using liquid chromatography-tandem mass spectrometry. Acepromazine was also incubated in vitro with whole equine blood and serum concentrations of the parent drug and metabolites determined. Acepromazine was quantitated for 24 hr following intravenous administration and 72 hr following oral and SL administration. Results of in vitro incubations with whole blood suggest additional metabolism by RBCs. The mean ± SEM elimination half-life was 5.16 ± 0.450, 8.58 ± 2.23, and 6.70 ± 2.62 hr following intravenous, oral, and SL administration, respectively. No adverse effects were noted and horses appeared sedate as noted by a decrease in chin-to-ground distance within 5 (i.v.) or 15 (p.o. and SL) minutes postadministration. The duration of sedation lasted 2 hr. Changes in heart rate were minimal.

Pharmacokinetic, Clinical, and Myeloid Marker Responses to Acepromazine Sedation in Arabian Camels

“…The calibration curve showed good linearity between 0.1 and 40 ng/ml. The recovery rate was 89.6 ± 11.6, consistent with the previously recorded recovery rate (11,12).…”

“…Similar to camels, acepromazine was previously shown to induce a non-significant lower body temperature in cats (1) but a significant decrease in rectal temperature after 1 h in sheep (31). Regarding the respiratory rate, acepromazine induced an initial decrease and then a gradual increase in horses (11) and an overall 36% reduction in pregnant cattle (7).…”

“…Increased heart rate was observed in treated camels (Figure 3). Acepromazine produced a similar increase in heart rate in monogastric animals such as cats (0.05 mg/kg) (20) and horses (0.1 mg/kg) (11). Tachycardia and hypotension seem to be conserved features of acepromazine use in ruminant and nonruminant animals.…”

“…The pharmacokinetics of acepromazine have been studied in several animal species, including dogs (10) and equines (11)(12)(13)(14). In the urine of horses, acepromazine and its metabolites can be detected for up to 48 h post intravenous injection (12).…”

“…The pharmacokinetics of acepromazine have been studied in several animal species, including dogs ( 10 ) and equines ( 11 – 14 ). In the urine of horses, acepromazine and its metabolites can be detected for up to 48 h post intravenous injection ( 12 ). Although the onset and the duration of acepromazine's effects in camels were 5 min and 2.3 ± 0.5 h, respectively ( 15 ), to our knowledge, the pharmacokinetics and pharmacodynamics of acepromazine administration in camels have not been assessed.…”