Lidocaine should be used with some caution in repeated high dosing because of lacking pharmacokinetic information during long term treatment. Lidocaine is metabolized by CYP1A2, with only a minor contribution from CYP 3A4. Lidocaine is not listed as an inducer or as a mechanism-based inhibitor of CYP enzymes, nor is there any evidence of lidocaine capacity for Cyp-inhibition in clinical use. Lidocaine is reported as used uneventfully by 68 patients, and thus strong clinical evidence points to lidocaine as probably not porphyrinogenic. There are two reports of possible activation of the disorder following the use of lidocaine, but the reports are poorly documented and are therefore not taken into account in the judgement of the porphyrinogenicity of lidocaine.

Lidocaine hydrochloride is an amide derivative of diethyl amino acetic acid. Lidocaine has a lipophilic aromatic ring attached to a hydrophilic amino group by an amide linkage.

Lidocaine is a local anaesthetic. In oral solutions it is used as a topical application for mouth and upper digestive tract anaesthesia.

Lidocaine is readily absorbed from mucous membranes, and the absorption will be higher if the mucosa in the area of application has been traumatised.

The primary metabolic pathway of lidocaine is CYP1A2 and, to a minor extent, CYP3A4 mediated N-deethylation to the active monoethylglycinexylidide (MEGX). MEGX is further de-ethylated to 2,6-xylidine and glycinexylidide. 2,6-xylidine is hydrolysed by CYP 2A6 to 4-hydroxy-xylidine, which is the major metabolite found in urine. In vitro studies suggest that CYP 3A4 may be an important contributor to the N-deethylation of lidocaine in high concentrations (above therapeutic concentrations) (Wang 2000). Found to be a week inhibitor of CYP 1A2 (Kobayashi 1998), and suggested as a competitive inhibitor of CYP1A2 by Wei (1999). In another study lidocaine was found to competitively inhibit N-monodesethylation of amioderone (with Ki = 120 µM) (Kobayashi 1998). Rendic (2002) reports that lidocaine is a substrate and an inhibitor of CYP1A2, a substrate for CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C18, CYP3A4 and an inhibitor and a substrate of CYP2D6. There is no evidence of lidocaine capacity for Cyp-inhibition in clinical use. Some studies have shown an accumulation of lidocaine or/and MEGX in continued administration of lidocaine (Miyabe 1999, Thomson 1987, Bauer 1982, Ngo 1997). One study report signs of CYP 3A4 TDI in rodent microsome experiments (Bensoussan 1994), but this has not been confirmed in human studies.

Lidocaine was found to increase the activity of delta-aminolaevulinic acid synthase in a rat liver model (Parikh, R.K. & Moore, M.R., 1978). Lidocaine was found to induce delta-aminolaevulinic acid synthase and to cause accumulation of porphyrins and cytochrom P450 in chick embryo livers in ovo (de Verneuil, H., Deybach, J.C. et al, 1982).

Thunell, S., study to be published: Uneventfully used (mainly in dental procedures) by 45 patients. After the completion of the study, one instance of possible activation of the disorder following the use of lidocaine for dental surgery in a middle-aged male carrier of AIP was reported (other precipitating factors can not be excluded).

Uneventful use reported in 1 patient with acute porphyria. Uneventful use is also reported after use of lidocaine under other ATC codes; N02BB02 used in 9 patients, N02BB52 used in 9 patients, C01BB01 used in 1 patient, and D04AB01 used in 3 patient. One report of an attack of acute porphyria following the use of lidocaine (N02BB02) in a male with active AIP, but the attack is poorly documented.