title: Acepromazine pharmacokinetics: a forensic perspective.
abstract: Acepromazine (ACP) is a useful therapeutic drug, but is a prohibited substance in competition horses. The illicit use of ACP is difficult to detect due to its rapid metabolism, so this study investigated the ACP metabolite 2-(1-hydroxyethyl)promazine sulphoxide (HEPS) as a potential forensic marker. Acepromazine maleate, equivalent to 30mg of ACP, was given IV to 12 racing-bred geldings. Blood and urine were collected for 7days post-administration and analysed for ACP and HEPS by liquid chromatography-mass spectrometry (LC-MS). Acepromazine was quantifiable in plasma for up to 3h with little reaching the urine unmodified. Similar to previous studies, there was wide variation in the distribution and metabolism of ACP. The metabolite HEPS was quantifiable for up to 24h in plasma and 144h in urine. The metabolism of ACP to HEPS was fast and erratic, so the early phase of the HEPS emergence could not be modelled directly, but was assumed to be similar to the rate of disappearance of ACP. However, the relationship between peak plasma HEPS and the y-intercept of the kinetic model was strong (P=0.001, r(2)=0.72), allowing accurate determination of the formation pharmacokinetics of HEPS. Due to its rapid metabolism, testing of forensic samples for the parent drug is redundant with IV administration. The relatively long half-life of HEPS and its stable behaviour beyond the initial phase make it a valuable indicator of ACP use, and by determining the urine-to-plasma concentration ratios for HEPS, the approximate dose of ACP administration may be estimated.
authors.affiliation: School of Animal and Veterinary Sciences, Charles Sturt University, Locked Bag 588, Wagga Wagga, NSW 2678, Australia.
authors.forename: Fiona I
authors.initials: FI
authors.lastname: Schneiders
authors.forename: Glenys K
authors.initials: GK
authors.lastname: Noble
authors.forename: Raymond C
authors.initials: RC
authors.lastname: Boston
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Dunstan
authors.forename: Martin N
authors.initials: MN
authors.lastname: Sillence
authors.forename: Andrew R
authors.initials: AR
authors.lastname: McKinney
mesh_terms: D000075:Acepromazine / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D000818:Animals; D019540:Area Under Curve; D018492:Dopamine Antagonists / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D005554:Forensic Medicine / Q000379:methods*; D006207:Half-Life; D006736:Horses / Q000097:blood / Q000378:metabolism*; D008297:Male; D011395:Promazine / Q000031:analogs & derivatives / Q000097:blood / Q000378:metabolism
chemical_list: C121957:2-(1-hydroxyethyl)promazine; D018492:Dopamine Antagonists; D000075:Acepromazine; D011395:Promazine