Source: FDA, National Drug Code (US) Revision Year: 2019
Prilocaine stabilizes the neuronal membrane by inhibiting the ionic fluxes required for the initiation and conduction of impulses, thereby effecting local anesthetic action.
When used for infiltration injection in dental patients, the time of onset of anesthesia averages less than 2 minutes with an average duration of soft tissue anesthesia of approximately 2 hours.
Based on electrical stimulation studies, 4% Citanest Plain Dental Injection provides a duration of pulpal anesthesia of approximately 10 minutes in maxillary infiltration injections. In clinical studies, this has been found to provide complete anesthesia for procedures lasting an average of 20 minutes.
When used for inferior alveolar nerve block, the time of onset of 4% Citanest Plain Dental Injection averages less than three minutes with an average duration of soft tissue anesthesia of approximately 2 ½ hours.
Excessive blood levels may cause changes in cardiac output, total peripheral resistance, and mean arterial pressure. These changes may be attributable to a direct depressant effect of the local anesthetic agent on various components of the cardiovascular system.
Information derived from diverse formulations, concentrations and usages reveals that prilocaine is completely absorbed following parenteral administration, its rate of absorption depending, for example, upon such factors as the site of administration and the presence or absence of a vasoconstrictor agent. Prilocaine is metabolized in both the liver and the kidney and excreted via the kidney. It is not metabolized by plasma esterases. Hydrolysis of prilocaine by amidases yields ortho-toluidine and N-proylalanine. Both of these compounds may undergo ring hydroxylation.
O-toluidine has been found to produce methemoglobin, both in vitro and in vivo (see ADVERSE REACTIONS).
Because prilocaine is metabolized in both the liver and kidneys, hepatic and renal dysfunction may alter prilocaine kinetics.
As with other local anesthetic agents, the plasma binding of prilocaine may be dependent on drug concentration. At 0.5 to 1.0 mg/mL it is 55% protein bound.
Prilocaine crosses the blood-brain and placental barriers, presumably by passive diffusion.
Factors such as acidosis and the use of CNS stimulants and depressants affect the CNS levels of prilocaine required to produce overt systemic effects. In the rhesus monkey, arterial blood levels of 20 mg/mL have been shown to be the threshold for convulsive activity.
Studies of prilocaine in animals to evaluate the carcinogenic and mutagenic potential or the effect on fertility have not been conducted.
Chronic oral toxicity studies of ortho-toluidine, a metabolite of prilocaine, in mice (150 to 4800 mg/kg) and rats (150 to 800 mg/kg) have shown that ortho-toluidine is a carcinogen in both species. The lowest dose corresponds to approximately 50 times the maximum amount of ortho-toluidine to which a 50 kg subject would be expected to be exposed following a single injection (8 mg/kg) of prilocaine.
Ortho-toluidine (0.5 mg/mL) showed positive results in Escherichia coli DNA repair and phage-induction assays. Urine concentrates from rats treated with ortho-toluidine (300 mg/kg, orally) were mutagenic for Salmonella typhimurium with metabolic activation. Several other tests, including reverse mutations in five different Salmonella typhimurium strains with or without metabolic activation and single strand breaks in DNA of V79 Chinese hamster cells, were negative.
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