title: Pharmacokinetics of Lidocaine Hydrochloride Administered with or without Adrenaline for the Paravertebral Brachial Plexus Block in Dogs.
abstract: Adrenaline is known to prolong the duration of local anesthesia but its effects on the pharmacokinetic processes of local anesthetic drugs are not fully understood. Our objective was to develop a compartmental model for quantification of adrenaline's impact on the pharmacokinetics of perineurally-injected lidocaine in the dog. Dogs were subjected to paravertebral brachial plexus block using lidocaine alone or adrenalinated lidocaine. Data was collected through a prospective, randomised, blinded crossover protocol performed over three periods. Blood samples were collected during 180 minutes following block execution. Compartmental pharmacokinetic models were developed and their goodness-of-fit were compared. The lowering effects of adrenaline on the absorption of lidocaine were statistically determined with one-sided tests. A one-compartment disposition model with two successive zero-order absorption processes best fitted our experimental data. Adrenaline decreased the peak plasma lidocaine concentration by approximately 60% (P < 0.001), decreased this local anesthetic's fast and slow zero-order absorption rates respectively by 50% and 90% (P = 0.046, and P < 0.001), which respective durations were prolonged by 90% and 1300% (P < 0.020 and P < 0.001). Lidocaine demonstrated a previously unreported atypical absorption profile following its paravertebral injection in dogs. Adrenaline decreased the absorption rate of lidocaine and prolonged the duration of its absorption.
authors.affiliation: Québec's Animal Pharmacology Research Group (GREPAQ), Department of Veterinary Biomedical Sciences, Université de Montréal, Saint-Hyacinthe, Québec, Canada.
authors.forename: Amélie
authors.initials: A
authors.lastname: Choquette
authors.affiliation: Québec's Animal Pharmacology Research Group (GREPAQ), Department of Veterinary Biomedical Sciences, Université de Montréal, Saint-Hyacinthe, Québec, Canada.
authors.forename: Eric
authors.initials: E
authors.lastname: Troncy
authors.affiliation: Québec's Animal Pharmacology Research Group (GREPAQ), Department of Veterinary Biomedical Sciences, Université de Montréal, Saint-Hyacinthe, Québec, Canada.
authors.forename: Martin
authors.initials: M
authors.lastname: Guillot
authors.affiliation: Faculty of Pharmacy, Université de Montréal, Montréal, Québec, Canada.
authors.forename: France
authors.initials: F
authors.lastname: Varin
authors.affiliation: Québec's Animal Pharmacology Research Group (GREPAQ), Department of Veterinary Biomedical Sciences, Université de Montréal, Saint-Hyacinthe, Québec, Canada.
authors.forename: Jérôme R E
authors.identifier: http://orcid.org/0000-0001-5046-7926
authors.initials: JR
authors.lastname: Del Castillo
mesh_terms: D000779:Anesthetics, Local / Q000008:administration & dosage; D000818:Animals; D065527:Brachial Plexus Block / Q000379:methods; D004285:Dogs; D004837:Epinephrine / Q000008:administration & dosage*; D007700:Kinetics; D008012:Lidocaine / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D008962:Models, Theoretical; D014662:Vasoconstrictor Agents / Q000008:administration & dosage / Q000493:pharmacokinetics
chemical_list: D000779:Anesthetics, Local; D014662:Vasoconstrictor Agents; D008012:Lidocaine; D004837:Epinephrine