Pharmacokinetics and metabolism of lidocaine HCl 2% with epinephrine in horses following a palmar digital nerve block.
Abstract: Lidocaine is a local anesthetic that is sometimes administered in combination with epinephrine. The addition of epinephrine increases the time lidocaine remains at the site of administration, thus prolonging the duration of effect. Due to their potential to prevent the visual detection of lameness, the administration of local anesthetics is strictly regulated in performance and racehorses. Recent reports of positive regulatory findings for lidocaine in racehorses suggests a better understanding of the behavior of this drug is warranted. The objective of the current study was to describe serum and urine concentrations and the pharmacokinetics of lidocaine and its primary metabolites following administration in combination with epinephrine, as a palmar digital nerve block in horses. Twelve horses received a single administration of 1 mL of 2% lidocaine HCl (20 mg/horse) with epinephrine 1:100,000, over the palmar digital nerve. Blood samples were collected up to 30 h and urine samples up to 48 h post administration. Lidocaine and metabolite concentrations were determined by liquid chromatography- mass spectrometry and pharmacokinetic (non-compartmental and compartmental) analysis was performed. Results: Serum concentrations of lidocaine and 3-hydroxylidocaine were above the LOQ of the assay at 30 h post administration and monoethylglycinexylidide (MEGX) and glycinexylidide (GX) were below detectable levels by 24 and 48 h, respectively. In urine, lidocaine, MEGX and GX were all non-detectable by 48 h post administration while 3-hydroxylidocaine was above LOQ at 48 h post administration. The time of maximal concentration for lidocaine was 0.26 h (median) and the terminal half-life was 3.78 h (mean). The rate of absorption (Ka) was 1.92 1/h and the rate of elimination (Kel) was 2.21 1/h. Conclusions: Compared to previous reports, the terminal half-life and subsequent detection time observed following administration of lidocaine in combination with epinephrine is prolonged. This is likely due to a decrease in systemic uptake of lidocaine because of epinephrine induced vasoconstriction. Results of the current study suggest it is prudent to use an extended withdrawal time when administering local anesthetics in combination with epinephrine to performance horses.
© 2023. The Author(s).
Publication Date: 2023-10-30 PubMed ID: 37904169PubMed Central: PMC10614310DOI: 10.1186/s12917-023-03787-xGoogle Scholar: Lookup
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Summary
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This research examines how lidocaine, a local anesthetic used in combination with epinephrine, is absorbed, metabolized, and eliminated in horses following a palmar digital nerve block, with a primary focus on its serum and urine concentrations and pharmacokinetics. The researchers suggest that the prolonged detection time of lidocaine when combined with epinephrine is due to a decrease in systemic uptake caused by the vasoconstriction induced by epinephrine.
Experiment Overview
- This study involved the administration of lidocaine in combination with epinephrine to twelve horses, with concentrations of lidocaine and its main metabolites measured in the animals’ serum and urine.
- In the experiment, each horse received a single administration of 1 mL of 2% lidocaine HCl, equivalent to 20 mg per horse, combined with epinephrine at a concentration ratio of 1:100,000.
- This was given over the palmar digital nerve, with blood samples collected up to 30 hours after administration, and urine samples collected up to 48 hours afterward.
- The researchers used liquid chromatography-mass spectrometry to determine the concentrations of lidocaine and its metabolites, and performed a pharmacokinetic analysis.
Key Findings
- In the serum, lidocaine and 3-hydroxylidocaine remained above the lowest level of quantitation (LOQ) of the assay even 30 hours after the administration.
- Meanwhile, the levels of monoethylglycinexylidide (MEGX) and glycinexylidide (GX) dropped below the detection levels after 24 and 48 hours, respectively.
- In the urine samples, lidocaine, MEGX, and GX were all undetectable after 48 hours post-administration, while 3-hydroxylidocaine remained above the LOQ even 48 hours after administration.
- The time to reach the highest concentration for lidocaine was observed to be around 0.26 hours on average, and the average terminal half-life was 3.78 hours.
- The absorption rate (Ka) stood at 1.92 per hour, while the elimination rate (Kel) was 2.21 per hour.
Insights and Conclusion
- The pharmacokinetics of lidocaine differ when it’s used in combination with epinephrine, as compared to its use alone. This is primarily attributed to the vasoconstriction induced by epinephrine, which decreases the systemic uptake of lidocaine, resulting in a prolonged terminal half-life and detection time.
- This research suggests that more careful consideration of withdrawal times is required when administering local anesthetics like lidocaine in combination with epinephrine in performance horses, given that detection times are longer than previously thought.
Cite This Article
APA
Knych HK, Katzman S, McKemie DS, Arthur RM, Blea J.
(2023).
Pharmacokinetics and metabolism of lidocaine HCl 2% with epinephrine in horses following a palmar digital nerve block.
BMC Vet Res, 19(1), 225.
https://doi.org/10.1186/s12917-023-03787-x Publication
Researcher Affiliations
- K.L. Maddy Equine Analytical Chemistry Laboratory, (Pharmacology Section) School of Veterinary Medicine, University of California, Davis, 620 West Health Science Drive, Davis, CA, 95616, USA. hkknych@ucdavis.edu.
- Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, CA, USA. hkknych@ucdavis.edu.
- Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, CA, USA.
- K.L. Maddy Equine Analytical Chemistry Laboratory, (Pharmacology Section) School of Veterinary Medicine, University of California, Davis, 620 West Health Science Drive, Davis, CA, 95616, USA.
- School of Veterinary Medicine, University of California, Davis, CA, USA.
- School of Veterinary Medicine, University of California, Davis, CA, USA.
MeSH Terms
- Horses
- Animals
- Anesthetics, Local / pharmacology
- Lidocaine
- Epinephrine
- Nerve Block / veterinary
Conflict of Interest Statement
The authors declare no competing interests.
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