Pharmacological properties : תכונות פרמקולוגיות

Pharmacodynamic Properties

5.1   Pharmacodynamic properties
Pharmacotherapeutic group: Anaesthetics, local, ATC code N01B B58 Articaine HCl 4% and Epinephrine 1:100,000 contains articaine which is a local anaesthetic of the amide type for dentistry and leads to a reversible inhibition of the irritability of vegetative, sensory and motor nerve fibres. The blocking of voltage dependent Na+ channels on the membrane of the nerve fibre is supposed to be the mechanism of effect of articaine. The rapid onset of anaesthesia - latency period of 1 - 3 minutes - the reliable effect with strong analgesic effect and good local tolerability are characteristic. The duration of effect of Articaine HCl 4% and Epinephrine 1:100,000 in pulpal anaesthesia lasts at least 75 minutes, and in soft-tissue anaesthesia 120 to 240 minutes.
Epinephrine leads locally to vasoconstriction, whereby the absorption of articaine is delayed. The result is a higher concentration of the local anaesthetic at the site of effect over a longer period, as well as the reduction in the occurrence of systemic adverse side effects.

Pharmacokinetic Properties

5.2) Pharmacokinetic properties
• Articaine
Absorption: In three published clinical studies describing the pharmacokinetic profile of the combination articaine hydrochloride 40 mg/ml with epinephrine 10 or 5 micrograms/ml, Tmax values were between 10 and 12 minutes, with Cmax values ranging from 400 to 2100 ng/ml.
In clinical trials performed in children, Cmax was 1382 ng/ml and Tmax 7.78 min following infiltration of a dose of 2 mg/kg body weight.

Distribution: High protein binding of articaine was observed with human serum albumin (68.5-80.8%), and α/β-globulins (62.5-73.4%). Binding to γ-globulin (8.6-23.7%) was much lower. Epinephrine is a vasoconstrictor added to articaine to slow down absorption into the systemic circulation and thus prolong maintenance of active articaine tissue concentration. The volume of distribution in plasma was about 4 l/kg.

Biotransformation: Articaine is subject to hydrolysis of its carboxyl group by unspecific esterases in the tissue and in blood. Since this hydrolysis is very fast, about 90% of articaine is inactivated by this way. Articaine is additionally metabolised in the liver microsomes. Articainic acid is the major product of cytochrome P450-induced metabolism of articaine, further metabolised to form articainic acid glucuronide.

Elimination: Following dental injection, the elimination half-life of articaine was c.a. 20-40 min. In a clinical trial, plasma concentrations of articaine and articainic acid were shown to decrease rapidly following submucosal injection.
Very little articaine was detected in plasma from 12 to 24 hours following injection. More than 50% of the dose was eliminated in the urine, 95% as articainic acid, within 8 hours of administration. Within 24 hours, approximately 57% (68 mg) and 53% (204 mg) of the dose was eliminated in the urine. Renal elimination of unchanged articaine accounted for only about 2% of total elimination.