title: Mepivacaine: its pharmacological effects and their relationship to analytical findings in the horse.
abstract: Mepivacaine is a local anaesthetic drug that is widely used in equine medicine and is classified by the Association of Racing Commissioners International (ARCI) as a Class 2 foreign substance that may cause regulators to impose significant penalties if residues are identified in post-race urine samples. Therefore, an analytical/pharmacological database was developed for this agent and its metabolites. Using an abaxial sesamoid local anaesthetic model, it was determined that the highest no-effect dose (HNED) for its local anaesthetic effect was 2 mg. Using enzyme-linked immunosorbent assay (ELISA) screening, it was determined that subcutaneous (s.c.) administration of the HNED of mepivacaine to eight horses yielded a peak urinary concentration of apparent mepivacaine of 63 ng/mL 2 h after injection. The major identified metabolite recovered from equine urine after dosing with mepivacaine is 3-hydroxymepivacaine. Therefore, 3-hydroxymepivacaine was synthesized, purified and characterized, and a quantitative mass spectrometric method was developed for this metabolite as isolated from horse urine. Following subcutaneous injection of the HNED of mepivacaine, the concentration of 3-hydroxymepivacaine recovered from horse urine reached a peak of about 64.6 ng/mL at 4 h after administration as measured by GC/MS. The concentration of mepivacaine or its metabolites after administration of a HNED dose are detectable by mass spectral techniques. Within the limits of this research, the study suggests that recovery of concentrations less than about 65 ng/mL of 3-hydroxymepivacaine from post-race urine samples may not be associated with a recent LA effect of mepivacaine.
authors.affiliation: Maxwell H. Gluck Equine Research Center and the Department of Veterinary Science, University of Kentucky, Lexington 40506-0099, USA.
authors.forename: J D
authors.initials: JD
authors.lastname: Harkins
authors.forename: W
authors.initials: W
authors.lastname: Karpiesiuk
authors.forename: W E
authors.initials: WE
authors.lastname: Woods
authors.forename: A
authors.initials: A
authors.lastname: Lehner
authors.forename: G D
authors.initials: GD
authors.lastname: Mundy
authors.forename: W A
authors.initials: WA
authors.lastname: Rees
authors.forename: L
authors.initials: L
authors.lastname: Dirikolu
authors.forename: S
authors.initials: S
authors.lastname: Bass
authors.forename: W G
authors.initials: WG
authors.lastname: Carter
authors.forename: J
authors.initials: J
authors.lastname: Boyles
authors.forename: T
authors.initials: T
authors.lastname: Tobin
mesh_terms: D000779:Anesthetics, Local / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D001711:Biotransformation; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006736:Horses / Q000502:physiology*; D006868:Hydrolysis; D008619:Mepivacaine / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D009407:Nerve Block; D019055:No-Observed-Adverse-Effect Level
chemical_list: D000779:Anesthetics, Local; D008619:Mepivacaine