Mepivacaine: Its pharmacological effects and their relationship to analytical findings in the horse

J. D. Harkins, W. Karpiesiuk, W. E. Woods, A. Lehner, G. D. Mundy, W. A. Rees, Levent Dirikolu, S. Bass, W. G. Carter, J. Boyles, T. Tobin

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)107-121
Number of pages15
JournalJournal of Veterinary Pharmacology and Therapeutics
Volume22
Issue number2
DOIs
StatePublished - Jun 7 1999

ASJC Scopus subject areas

  • Pharmacology
  • veterinary(all)

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    Harkins, J. D., Karpiesiuk, W., Woods, W. E., Lehner, A., Mundy, G. D., Rees, W. A., Dirikolu, L., Bass, S., Carter, W. G., Boyles, J., & Tobin, T. (1999). Mepivacaine: Its pharmacological effects and their relationship to analytical findings in the horse. Journal of Veterinary Pharmacology and Therapeutics, 22(2), 107-121. https://doi.org/10.1046/j.1365-2885.1999.00189.x