The pharmacokinetics and effects of meloxicam, gabapentin, and flunixin in postweaning dairy calves following dehorning with local anesthesia

Abstract

Approved analgesic compounds in cattle are not currently available in the United States due to the lack of validated pain assessment methods and marker residue depletion studies. In this study, we compared the pharmacokinetic parameters and effect of preemptive analgesics administered to calves subjected to dehorning with local anesthesia. Holstein steers were randomly assigned to receive one of the following treatments per os (PO) or intravenously (IV) (n = 8/group): meloxicam (1 mg/kg PO), gabapentin (15 mg/kg PO), meloxicam (1 mg/kg), and gabapentin (15 mg/kg) PO, flunixin (2.2 mg/kg IV), or a placebo. Plasma drug, haptoglobin, substance P (SP) concentrations, serum cortisol concentrations, ocular thermography, mechanical nociceptive threshold (MNT), and average daily gain (ADG) were evaluated. Data were analyzed using mixed-effects models and noncompartmental pharmacokinetic analysis. Meloxicam, gabapentin, and meloxicam with gabapentin at the present doses did not reduce cortisol concentrations. Analgesic-treated calves had significantly lower plasma SP concentrations and improved ADG compared with controls. Flunixin calves had reduced circulating cortisol compared with controls. Meloxicam-treated calves showed an increase in MNT at two horn bud sites compared with the other treatments. Analgesics improved ADG and reduced biomarkers of pain, but effects differed by compound and route of administration.

Effects of sample handling methods on substance P concentrations and immunoreactivity in bovine blood samples

“…Liquid chromatography-tandem mass spectrometry SP [1][2][3][4][5][6][7][8][9][10][11] Parent substance P molecule composed of 11 amino acids SP [3][4][5][6][7][8][9][10][11] Metabolite of substance P composed of the last 9 C-terminal amino acids SP [7][8][9][10][11] Metabolite of substance P composed of the last 5 C-terminal amino acids been evaluated as a response variable that may be more specific for the measurement of pain in animals. [3][4][5][6][7][8][9][10] Substance P is a biologically active peptide that has a role in neural transmission of nociceptive signals from peripheral sites to the CNS.…”

“…[3][4][5][6][7][8][9][10] Substance P is a biologically active peptide that has a role in neural transmission of nociceptive signals from peripheral sites to the CNS. 11 Substance P is released by peptidergic peripheral sensory nerve fibers at central synaptic junctions in the dorsal horn of the spinal cord and at peripheral nerve terminals, where the peptide has a role as a signaling molecule in the transmission of pain impulses and the induction of inflammation and central sensitization.…”

“…The substance P parent molecule is a peptide composed of 11 amino acids with an amidated carboxyl terminus (arginine-prolinelysine-proline-glutamine-glutamine-phenylalaninephenylalanine-glysine-leucine-ethionine-NH 2 ). Enzymes that cleave SP [1][2][3][4][5][6][7][8][9][10][11] include members of the serine and metalloprotease families: angiotensin I-converting enzyme, aminopeptidase, neutral endopeptidase, dipeptidyl peptidase IV, and postproline cleaving enzyme. 13,14 Enzymes of these classes require inhibitors with specific affinity for their catalytic sites; therefore, protection of SP [1][2][3][4][5][6][7][8][9][10][11] from enzymatic degradation may require at least 2 inhibitor types.…”

“…Enzymes that cleave SP [1][2][3][4][5][6][7][8][9][10][11] include members of the serine and metalloprotease families: angiotensin I-converting enzyme, aminopeptidase, neutral endopeptidase, dipeptidyl peptidase IV, and postproline cleaving enzyme. 13,14 Enzymes of these classes require inhibitors with specific affinity for their catalytic sites; therefore, protection of SP [1][2][3][4][5][6][7][8][9][10][11] from enzymatic degradation may require at least 2 inhibitor types. Various degradation products are derived from SP [1][2][3][4][5][6][7][8][9][10][11] and are named in accordance with the amino acids they contain.…”

Impact of oral meloxicam administered alone or in combination with gabapentin on experimentally induced lameness in beef calves1

“…The numerical difference in ADG between the MEL-GABA group and the PLBO group was surprising because both groups were less active than calves within the MEL group based on the pedometer results. It was recently reported that calves treated with MEL-GABA had a greater ADG after dehorning compared to calves receiving either MEL (P = 0.02) or GABA (P = 0.0006) alone (Glynn et al, 2013). This finding suggests the potential for a synergistic effect of these compounds for improving the growth and performance of calves after a painful event but further research is needed before widespread use can be recommended.…”