Population pharmacokinetics of articaine with 1:200,000 epinephrine during third molar surgery and simulation of high-dose regimens

Publication date: 1 March 2018
Source:European Journal of Pharmaceutical Sciences, Volume 114
Author(s): Yoann Cazaubon, Cédric Mauprivez, Catherine Feliu, Laurent Binet, Olivier Oget, Claire Gozalo, Zoubir Djerada
Background and objectivesArticaine is more and more used in third molar surgery under local anesthesia (LA). The objectives of this analysis were to characterize the pharmacokinetics of articaine for this type of surgery and to simulate dosing regimens.MethodsNon-linear mixed-effects modeling conducted in Monolix 4.4.0 was used to describe articaine plasma concentration-time data from 20 patients. Monte Carlo simulations were then performed to evaluate the probability of cardiotoxic target attainment (PCTA) of various dosage regimens.ResultsArticaine concentration data were best described by a linear one-compartment model, with an additional depot compartment for submucosal route with a zero-order transfer to central compartment. Age and gender were found to influence duration transfer (Tk0) and elimination rate constant (Ke), respectively. Simulated maximum recommended dose regimen (7mg/kg) had a PCTA of 0%. Simulated higher doses of 10mg/kg and 15mg/kg had a PCTA of 0% and about 1–4%, respectively.ConclusionsThe model adequately described the articaine pharmacokinetics. This is the first PK model qualified for articaine administered by submucosal route. The simulations suggest that maximum recommended dose regimen is safe concerning the cardiotoxicity in healthy patients.

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