N01BB03 - Mepivacaine |
Propably not porphyrinogenic |
PNP |
Rationale
Mepivacaine differs structurally from the bupivacaine only in the in the substitution of a methyl group for the N-butyl group. Sharing the structural metabolic prerequisites of the non-porphyrogenic drug bupivacaine gives theoretical grounds to classify mepivacaine as probably not porphyrinogenic. Uneventful use has been reported in 13 patients.
Chemical description
Mepivacaine hydrochloride is a local anaesthetic of the amide type. Mepivacaine differs structurally from the non-porphyrogenic drug bupivacaine only in the in the substitution of a methyl group for the N-butyl group.
Therapeutic characteristics
Local anaesthetic. Administration in combination with epinephrine (adrenaline) (not porphyrogenic) prolongs the effect of mepivacaine, and reduces hepatic exposure and the risk of systemic reactions.
Hepatic exposure
Unknown.
Metabolism and pharmakokinetics
Mepivacaine is rapidly metabolised in the liver and less than 10% of a dose is reported to be excreted unchanged in the urine. Over 50% of a dose is excreted as metabolites into the bile but these probably undergo enterohepatic circulation as only small amounts appear in the faeces. Several metabolites are also excreted via the kidneys and include glucuronide conjugates of hydroxy compounds and an N-demethylated compound, 2´,6´-pipecoloxylidide. The drug has not been found to be an inducer or irreversible inhibitor of drug metabolizing cytochrome P450 species (Rendic, 2002) and is therefore most probably devoid of capacity for ALAS1-induction. Sharing the structural metabolic prerequisites of bupivacaine, the probability is that this substance will not take part in ALAS1-induction needed for porhyrogenic action.
Personal communication
Thunell, S., study to be published: 11 patients exposed without porphyric adverse reaction reported. Andersson:
Published experience
Uneventful use reported in a case report of one 55 year old AIP woman devoid of clinical symptoms but with elevated PBG levels. Twenty ml of 1% mepivacaine was injected as postoperative pain control following a hip replacement surgery (Hiraki, T., Oishi, K. et al, 2001). Uneventful use in one 32 year old HCP woman who received routine dental local anesthesia consisting of 2% mepivacaine with 1:20,000 levonordefrin. (Moore, A.W.,& Coke,J.M., 2000).
References
- Scientific articles
- de Verneuil,H., Deybach,J.C. et al. Study of anaesthetic agents for their ability to elicit porphyrin biosynthesis in chick embryo liver. Biochem Pharmacol 1982; 32: 1011-18. #1192
- Hiraki,T., Oishi,K. et al. [Anesthetic management of a patient with a history of acute intermittent porphyria and an elevation of urinary porphobilinogen]. Masui 2001;50: 882-5. #2498
- Moore AW 3rd, Coke JM. Acute porphyric disorders.Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2000;90(3):257-62. #2499
- Rendic, S. Summery of information on human CYP enzymes: human P450 metabolism. Drug metabolism reviews 2002; 34(1&2), 83-448. #1025
- Thunell, S., Evidence-based porphyrogenicity assessment of seven local anasthetics (2009, to be published). #2502
- Drug reference publications
- Sweetman SC, editor. Martindale: The complete drug reference. Mepivacaine Hydrochloride. Pharmaceutical Press 2009. #2501
- Summary of Product Characteristics
- Norwegian medicines agency. Summary of Product Characteristics (SPC). Carbocain Dental. #2500
Similar drugs
© NAPOS 2024