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. The systemic availability of lidocaine after restricted dermal use is usually low.

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 anesthetic. In dermatological preparations lidocaine is used for the symptomatic relief of pain, itching or irritation of the skin or mucous membranes. It can be administered in topical formulations like ointment, gel or liniment for conditions like superficial skin wounds, insect bites, burns, herpes genitalis, and anal lesions or before various medical procedures.

The plasma concentration of lidocaine is dependent on dose, administration method and vascularity of the site of administration. Whether the site of application has a traumatised or intact surface will also affect the absorption and systemic availability of the drug. Lidocaine is readily absorbed from mucous membranes and through damaged skin The hepatic exposure of lidocaine after restricted dermal use is probably not significant.. Systemic plasma concentrations after repeted anorectal administration of 5 % lidocaine ointment was found to be below uM (Zimmermann 2007).

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 3 patients 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 R02AD02 used in 1 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.