Dose-dependent pharmacokinetics of ropivacaine in anesthetized rabbits : absence of changes in protein binding
Article [Version publiée]
Fait partie de
Journal of veterinary science and animal husbandry ; vol. 7, no 1.Éditeur·s
Annex PublishersAffiliation
Résumé·s
Objective: The primary objectives of this study were to investigate the in vivo pharmacokinetics and in vitro plasma protein binding of
ropivacaine at the concentration range observed after intravenous administration of different doses in anesthetized rabbits.
Study design: Prospective experimental study
Animals: Thirteen New Zealand White rabbits
Methods: Rabbits were anesthetized with isoflurane. Different doses (0.62 to 6.52 mg/kg) of 0.5 % plain ropivacaine hydrochloride were
administered and arterial blood sampled at frequent intervals up to 10 hours. Ropivacaine plasma concentrations were determined by
high performance liquid chromatography. Pharmacokinetic analysis of individual data sets was performed using non-compartmental
approach to calculate area under the plasma concentration–time curve from time zero to infinity (AUC0–inf). In vivo pharmacokinetics
linearity was verified using analyses of variance for between group comparisons of the effect of dose on the AUC0–inf normalized by the
dose. A population pharmacokinetic model was developed to describe ropivacaine disposition after intravenous administration in the
linear range of dose in anesthetized rabbits. Determination of protein binding was performed, under controlled temperature and pH
conditions, in plasma samples spiked extemporaneously with 3
H-ropivacaine and unlabeled ropivacaine (2.5 and 3500 ng/ml) using
an ultrafiltration method.
Results: At intravenous doses higher than 3.67 mg/kg, dose-dependent changes in ropivacaine systemic clearance were observed. In
contrast, protein binding was found to be concentration independent in the tested range.
Conclusions and clinical relevance: In anesthetized rabbits, saturation of ropivacaine plasma protein binding is not the mechanism
responsible for the pharmacokinetic nonlinearity of ropivacaine observed at intravenous doses higher than 3.67 mg/kg. Disposition
parameters obtained in our study will enable accurate characterization of ropivacaine pharmacokinetics after a peripheral nerve block.
Collections
Ce document diffusé sur Papyrus est la propriété exclusive des titulaires des droits d'auteur et est protégé par la Loi sur le droit d'auteur (L.R.C. (1985), ch. C-42). Il peut être utilisé dans le cadre d'une utilisation équitable et non commerciale, à des fins d'étude privée ou de recherche, de critique ou de compte-rendu comme le prévoit la Loi. Pour toute autre utilisation, une autorisation écrite des titulaires des droits d'auteur sera nécessaire.