Serum concentrations of lidocaine and its metabolites after prolonged infusion in healthy horses

Abstract

Summary Reasons for performing study: Continuous‐rate infusions (CRI) of lidocaine are often used for prolonged duration but, to date, only limited time/concentration relationships administered as a short term (24 h) CRI have been reported. Objective: To determine the time/concentration profile of lidocaine and its active metabolites glycinexylidide (GX) and monoethylglycinexylidide (MEGX) during a 96 h lidocaine infusion. Methods: Lidocaine was administered to 8 mature healthy horses as a continuous rate infusion (0.05 mg/kg bwt/min) for 96 h. Blood concentrations of lidocaine, GX and MEGX were determined using high performance liquid chromatography during and after discontinuation of the infusion. Results: Serum lidocaine concentrations reached steady state by 3 h and did not accumulate thereafter. Concentrations were above the target therapeutic concentration (980 ng/ml) only at 6 and 48 h, and did not reach the range described as potentially causing toxicity (>1850 ng/ml) at any time. MEGX did not accumulate over time, while the GX accumulated significantly up to 48 h and then remained constant. The serum concentrations of lidocaine, MEGX and GX were below the limit of detection within 24 h of discontinuation of the infusion. None of the horses developed any signs of lidocaine toxicity during the study. Conclusions: The metabolism of lidocaine was not significantly impaired by prolonged infusion and no adverse effects were observed. Prolonged infusions appear to be safe in normal horses but the accumulation of GX, a potentially toxic active metabolite, is cause for concern. Clinical relevance: Although the toxic level of GX has not yet been determined, such accumulation could lead potentially to adverse side effects and it is important to consider this potential for accumulation when utilising prolonged lidocaine infusions.

Lidocaine Metabolites Inhibit Glycine Transporter 1

“…For these experiments, a clinically relevant concentration of lidocaine (4 M) was combined with a fixed concentration ratio of its metabolites (MEGX 2.5 M, GX 0.3 M, EG 30 M) to mimic the clinical situation, especially after continuous application of lidocaine. [32][33][34] At the lowest glycine concentration (10 M), glycine uptake was very low and therefore no inhibition could be detected either with ALX5407 as the positive control or with the combination of lidocaine and the three major metabolites. With increasing glycine concentrations (25-100 M), glycine uptake increased considerably ( fig.…”

Efeito da lidocaína venosa intraoperatória sobre dor e interleucina‐6 plasmática em pacientes submetidas a histerectomia

“…Estudos experimentais têm evidenciado que MEGX, mas não a lidocaína, aumentou a atividade glicinérgica (neurotransmissão inibitória) por meio do bloqueio de GlyT1 (transportador de glicina 1) no sistema nervoso central em concentrações clinicamente relevantes. 16,29,30 Em nosso estudo, a concentração média de MEGX alcançada foi de 0,55 g.ml −1 cinco horas após o início da operação, semelhante ao nível que leva à inibição in vitro do transporte de glicina e que foi observado durante a infusão contínua de lidocaína. 29 Ao contrário de alguns estudos anteriores, 6,7 a lidocaína não apresentou efeito poupador de morfina e isoflurano em nosso estudo.…”

Efecto de la lidocaína venosa intraoperatoria sobre el dolor e interleucina-6 plasmática en pacientes sometidas a histerectomía

“…Estudios experimentales han evidenciado que MEGX, pero no así la lidocaína, aumentó la actividad glicinérgica (neurotransmisión inhibitoria), por medio del bloqueo de GlyT1 (transportador de glicina 1) en el sistema nervioso central en concentraciones clínicamente relevantes 16,29,30 . En nuestro estudio, la concentración media de MEGX alcanzada fue de 0,55 g/ml −1 5 h después del inicio de la operación, similar al nivel que conduce a la inhibición in vitro del transporte de glicina y que se observó durante la infusión continua de lidocaína 29 .…”