Pharmacokinetics and Cardiovascular Effects of Articaine with 1:100,000/1:200,000 Epinephrine

Objectives: This study compared the pharmacokinetics and cardiovascular effects of 4% articaine plus 1:200,000 epinephrine (A200) and 4% articaine plus 1:100,000 epinephrine (A100) following the injection of 11.9 ml of solution. Methods: Fourteen normal healthy volunteers entered this double-blind, randomized, two-way crossover clinical trial. Over a period of 8 minutes one cartridge of local anesthetic was injected at each of the following sites; maxillary right first molar, maxillary left first molar, maxillary right first premolar, maxillary left first premolar, right inferior alveolar block, left inferior alveolar block; and then one half cartridge for each mandibular buccal infiltration. Blood sampling was performed at 8, 10, 15, 20, 25, 30, 40, 50, 60, 90, and 120 minutes after the initiation of the first injection. Non-invasive acoustic tonometry assessed HR, SBP, DBP, MAP, SV, CO, small and large artery elasticity and SVR at baseline and then every 10 minutes after the initiation of the first injection. Subjective ratings of anesthesia intensity were performed at the same time points. Adverse reactions were recorded when and if they occurred. Results: There were no significant differences in Cmax or Tmax for the two formulations; 2145 ng/ml and 0.37 hours for A200 and 2037 ng/ml and 0.36 hrs for A100 (paired t-test). At 10 minutes post-dose, HR, SBP and CO were significantly greater (p < 0.05) for A100 (78.2 BPM, 130.6 mm Hg and 6.35 L/min) then A200 (69.6 BPM, 124.8 mm Hg and 6.20 L/min). Anesthetic success rates were similar between both solutions. Five subjects experienced a total of six adverse events. Only two were judged to be drug related. Conclusions: At doses approaching MRDs, both A200 and A100 were well tolerated with most cardiovascular differences occurring in the first 10 minutes following injection. Supported by a grant from Novocol Pharmaceutical of Canada.