Following dental injection by the submucosal route of an articaine solution containing 1:200,000 epinephrine, articaine reaches peak blood concentration about 25 minutes after a single dose injection and 48 minutes after three doses. Peak plasma levels of articaine achieved after 68 and 204 mg doses are 385 and 900 ng/mL, respectively.
Approximately 60 to 80% of articaine HCl is bound to human serum albumin and γ-globulins at 37°C in vitro.
Articaine HCl is rapidly metabolized by plasma carboxyesterase to its primary metabolite, articainic acid, which is inactive. In vitro studies show that the human liver microsome P450 isoenzyme system metabolizes approximately 5% to 10% of available articaine with nearly quantitative conversion to articainic acid.
The elimination half-life of articaine is about 1.8 hours and that of articainic acid is about 1.5 hours. Articaine is excreted primarily through urine with 53 - 57% of the administered dose eliminated in the first 24 hours following submucosal administration. Articainic acid is the primary metabolite in urine. A minor metabolite, articainic acid glucuronide, is also excreted in urine. Articaine constitutes only 2% of the total dose excreted in urine.
Effect of Age
No studies have been performed to evaluate the pharmacokinetics of Septocaine® injection in geriatric or pediatric subjects.
There is insufficient information to determine whether the pharmacokinetics of Septocaine® injection differs by race.
Renal and Hepatic Insufficiency
No studies have been performed with Septocaine® injection in patients with renal or hepatic dysfunction.
Mechanism of action
Articaine HCl is a member of the amino amide class of local anesthetics. Local anesthetics block the generation and conduction of nerve impulses, presumably by increasing the threshold for electrical excitation in the nerve, by slowing the propagation of the nerve impulse, and by reducing the rate of rise of the action potential. In general, the progression of anesthesia is related to the diameter, myelination and conduction velocity of the affected nerve fibers. Clinically, the order of loss of nerve function is as follows: (1) pain, (2) temperature, (3) touch, (4) proprioception, and (5) skeletal muscle tone. Epinephrine is a vasoconstrictor added to articaine HCl to slow absorption into the general circulation and thus prolong maintenance of an active tissue concentration.
The onset of anesthesia following administration of Septocaine® has been shown to be within 1 to 6 minutes of injection. Complete anesthesia lasts approximately 1 hour.
Administration of articaine HCl with epinephrine results in a 3- to 5-fold increase in plasma epinephrine concentrations compared to baseline; however, in heathly adults it does not appear to be associated with marked increases in blood pressure or heart rate, except in the case of accidental intravascular injection (See WARNINGS).
Three randomized, double-blind, active-controlled studies were designed to evaluate effectiveness of Septocaine® as a dental anesthetic. A total of 882 patients received Septocaine®. Of these, 7% were between 4 and 16 years old, 87% were between 17 and 65 years old, and 6% were at least 65 years old. In addition, 53% of patients were female and 47% were male, with a racial/ethnic distribution of 73% white, 11% Hispanic, 8% black, 5% Asian, and 3%"other" races/ ethnicities. These patients underwent simple dental procedures such as single uncomplicated extractions, routine operative procedures, single apical resections, and single crown procedures, and complex dental procedures such as multiple extractions, multiple crowns and/or bridge procedures, multiple apical resections, alveolectomies, muco-gingival operations, and other surgical procedures on the bone. Septocaine™ was administered as submucosal infiltration and/or nerve block. Efficacy was measured immediately following the procedure by having the patient and investigator rate the patient's procedural pain using a 10 cm visual analog scale (VAS), in which a score of zero represented no pain, and a score of 10 represented the worst pain imaginable.
Mean patient and investigator VAS pain scores were 0.3 - 0.4 cm for simple procedures and 0.5 - 0.6 cm for complex procedures. These values are summarized in Table 1.
Table 1. Summary of VAS Pain Scores
(articaine HCl 4% with epinephrine 1:100,000)
|Simple procedures||Complex procedures|
|Number of patients||674||207|
|Investigator score (cm)|
|Range||0 - 9.0||0 - 7.3|
|Patient score (cm)|
|Range||0 - 8.0||0 - 8.7|