Pharmacokinetics of articaine hydrochloride and its metabolite articainic acid after subcutaneous administration in red deer (Cervus elaphus)

Abstract

The LC-MS method used for the quantification of articaine and its metabolite articainic acid in the plasma of red deer was simple, accurate and sensitive. Articaine hydrochloride was rapidly absorbed, hydrolysed to its inactive metabolite articainic acid, and eliminated following S/C administration as a ring block in red deer. These favourable pharmacokinetic properties suggest that articaine hydrochloride should be tested for efficacy as a local anaesthetic in red deer for removal of velvet antlers. Further studies to evaluate the safety and residues of articaine hydrochloride and articainic acid are required before articaine can be recommended for use as a local anaesthetic for this purpose.

Pharmacokinetics, efficacy and convulsive dose of articaine hydrochloride in goat kids

“…Rapid elimination has also been reported in deer following subcutaneous administration (Venkatachalam et al 2018a) and following various routes of administration in humans (Oertel et al 1997). By comparison, the half-lives of lignocaine (1.71 ± 0.51 hours) and its active metabolite, monoethylglycinexylidide (3.22 ± 1.21 hours), following cornual nerve block of 1% lignocaine hydrochloride in goat kids were longer than articaine (Venkatachalam et al 2018b). Rapid elimination of articaine can be attributed to rapid hydrolysis by plasma esterases to articainic acid (Oertel et al 1997;Snoeck 2012).…”

“…The short elimination half-lives (t 1/2lz ) of articaine following IV administration (0.66 ± 0.14 hour) and subcutaneous administration (1.26 ± 0.34 hours) indicate that articaine was rapidly eliminated following systemic absorption. Rapid elimination has also been reported in deer following subcutaneous administration (Venkatachalam et al 2018a) and following various routes of administration in humans (Oertel et al 1997). By comparison, the half-lives of lignocaine (1.71 ± 0.51 hours) and its active metabolite, monoethylglycinexylidide (3.22 ± 1.21 hours), following cornual nerve block of 1% lignocaine hydrochloride in goat kids were longer than articaine (Venkatachalam et al 2018b).…”

“…It must be noted that rapid systemic absorption and greater lipid solubility may slow the onset of anaesthesia (Becker & Reed 2012). Rapid absorption has also been reported with lignocaine hydrochloride following cornual nerve block in goat kids (Venkatachalam et al 2018b). The C max of articaine following cornual nerve blockade was approximately a quarter of the concentration (2559 ± 413 ng mL e1 ) observed at 1 minute following IV administration of 8 mg kg e1 for over 60 seconds.…”

“…The results of the present study and the dose-ranging study suggest that doses up to 8 mg kg e1 may be safe for perineural injections in goat kids as the plasma concentrations following perineural injections would probably be much lower than the plasma concentrations following IV administration. Rapid absorption of articaine has also been reported in red deer (Venkatachalam et al 2018a) and humans (Snoeck 2012), which may result from its vasolidatory effect and greater lipid solubility (Becker & Reed 2006). It must be noted that rapid systemic absorption and greater lipid solubility may slow the onset of anaesthesia (Becker & Reed 2012).…”

“…Another important feature of articaine hydrochloride is the presence of an ester group within its structure, which allows rapid hydrolysis by plasma esterases to an inactive metabolite, articainic acid (Oertel et al 1997;Snoeck 2012). Pharmacokinetic studies in humans and red deer report that articaine hydrochloride is rapidly hydrolysed and eliminated from the systemic circulation (Oertel et al 1997;Snoeck 2012;Venkatachalam et al 2018a). Human studies suggest that articaine hydrochloride is more efficacious and safer than lignocaine, with a lower risk of systemic toxicity (Malamed et al 2001;Katyal 2010).…”