The pharmacokinetics and cardiovascular effects of high-dose articaine with 1:100,000 and 1:200,000 epinephrine

J Am Dent Assoc. 2006 Nov;137(11):1562-71. doi: 10.14219/jada.archive.2006.0092.


Objectives: The authors conducted a randomized, double-blind, two-way crossover clinical trial to compare the pharmacokinetics and cardiovascular effects of 11.9 milliliters of 4 percent articaine hydrochloride (HCl) plus 1:100,000 epinephrine (A100) with those of 11.9 mL of 4 percent articaine HCl plus 1:200,000 epinephrine (A200).

Methods: During two testing sessions, the authors administered injections of A100 and A200 over a seven-minute period (in one-cartridge doses unless otherwise noted): maxillary right first molar infiltration, maxillary left first molar infiltration, maxillary right first premolar infiltration, maxillary left first premolar infiltration, right inferior alveolar injection, left inferior alveolar injection, right long buccal infiltration (one-half cartridge) and left long buccal infiltration (one-half cartridge). They analyzed venous blood samples for articaine levels. They used noninvasive acoustic tonometry to measure a variety of cardiovascular parameters over a two-hour period.

Results: Plasma concentration curves of articaine over time were similar for both solutions, with peak concentrations and times to maximum concentration being 2,037 nanograms per milliliter and 22 minutes for A100 and 2,145 ng/mL and 22 minutes for A200. At the 10-minute point, the mean systolic blood pressure and heart rate were significantly elevated (P < .05) with A100 versus A200.

Conclusions: Maximum dose recommendations for the A100 solution also can be applied to the A200 solution. A200 produces less cardiovascular stimulation than does A100.

Clinical implications: A200 is as safe as A100, and may be preferable to A100 in patients with cardiovascular disease and in those taking drugs that reportedly enhance the systemic effects of epinephrine.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anesthesia, Dental / methods*
  • Anesthetics, Local / administration & dosage
  • Anesthetics, Local / blood
  • Anesthetics, Local / pharmacokinetics*
  • Cardiovascular System / drug effects*
  • Carticaine / administration & dosage
  • Carticaine / blood
  • Carticaine / pharmacokinetics*
  • Drug Interactions
  • Epidemiologic Methods
  • Epinephrine / administration & dosage
  • Epinephrine / pharmacology
  • Female
  • Humans
  • Male
  • Vasoconstrictor Agents / administration & dosage
  • Vasoconstrictor Agents / pharmacology


  • Anesthetics, Local
  • Vasoconstrictor Agents
  • Carticaine
  • Epinephrine