Disposition, bioavailability and clinical efficacy of orally administered acepromazine in the horse

Abstract

The pharmacokinetics and pharmacological efficacy of orally (p.o.) administered acepromazine were studied and compared with the intravenous (i.v.) route of administration in a cross-over study using six horses. The oral kinetics of acepromazine can be described by a two-compartment open model with first-order absorption. The drug was rapidly absorbed after p.o. administration with a half-life of 0.84 h, tmax of 0.4 h and Cmax of 59 ng/ml. The elimination was slower after p.o. administration (half-life 6.04 h) than after i.v. injection (half-life 2.6 h). The bioavailability of the orally administered drug formulation was 55.1%. After p.o. administration of 0.5 mg/kg acepromazine, the parameters of the sedative effect were similar to those obtained after i.v. injection of 0.1 mg/kg. The effect of the drug on blood cell count and haemoglobin content was similar after both p.o. administration and injection, while the effects on the parameters of penile prolapse and on the mean arterial blood pressure were less pronounced after p.o. administration than after injection. After p.o. administration, no significant effects on haematocrit-level as well as on the heart and respiratory rates were observed, while these parameters were significantly affected after injection. It is concluded that the high initial plasma level of the drug after i.v. injection may play a role in producing adverse effects of acepromazine.

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

“…administration. The disposition of acepromazine following intravenous administration has been described (Ballard, Shults, Kownacki, Blake, & Tobin, ; Hashem & Keller, ; Schneiders et al., ). It is characterized by a short elimination half‐life, which is largely attributable to rapid metabolism to 2‐(1‐hydroxyethyl) promazine (HEP) and 2‐(1‐hydroxyethyl) promazine sulfoxide (HEPS).…”

“…administration of drugs to veterinary patients is a convenient and less expensive means by which to administer drugs in horses. There is one report describing the pharmacokinetics of acepromazine following oral administration (Hashem & Keller, ). In that study, investigators administered a gel‐based acepromazine product to horses.…”

“…In that study, investigators administered a gel‐based acepromazine product to horses. Following administration of the gel formulation, acepromazine was rapidly absorbed (Hashem & Keller, ). The elimination half‐life was reported as 6.04 hr, which is slightly longer than what has been reported for intravenous administration (Hashem & Keller, ).…”

Acepromazine inhibits hERG potassium ion channels expressed in human embryonic kidney 293 cells

“…For veterinary use, the potency of acepromazine is species dependent: from 0.5 mg/kg in dogs to 5 mg/kg in horse, and the maximum plasma concentration (C max ) of acepromazine was ~0.19 µM when administered at a dose of 0.15 mg/kg [38] and the C max of ~0.18 µM when administered at a dose of 0.1 mg/kg [39] in horses. In a human toxicology case, after 8 hr of 950 mg acepromazine ingestion, the plasma acepromazine level was 0.19 µM [10].…”

Doppler ultrasonographic studies of the vascular resistance of the uterine artery in the mare associated with vasoactive and antikoagulative theory

“…Ein weiteres, direkt vasodilatatorisch wirkendes Präparat ist der α1-Rezeptor-Antagonist Acepromazin, der beim Pferd als Sedativum eingesetzt wird. Neben einem α-adrenerg verursachten Blutdruckabfall durch periphere Vasodilatation wird der Hämatokritwert herabgesetzt und damit die Fließfähigkeit des Blutes verbessert (Baxter et al,1989;Hashem und Keller, 1993). Die Ursache für den Hämatokritab-fall wird in der Induktion einer Milzrelaxation mit damit einhergehender erhöhter Erythrozytenspeicherfunktion gesehen (Parry und Anderson, 1983).…”