More methemoglobin is produced by benzocaine treatment than lidocaine treatment in human in vitro systems.

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Citation

Hartman NR, Mao JJ, Zhou H, Boyne MT 2nd, Wasserman AM, Taylor K, Racoosin JA, Patel V, Colatsky T

More methemoglobin is produced by benzocaine treatment than lidocaine treatment in human in vitro systems.

Regul Toxicol Pharmacol. 2014 Oct;70(1):182-8. doi: 10.1016/j.yrtph.2014.07.002. Epub 2014 Jul 8.

PubMed ID
25010377 [ View in PubMed
]
Abstract

The clinical use of local anesthetic products to anesthetize mucous membranes has been associated with methemoglobinemia (MetHba), a serious condition in which the blood has reduced capacity to carry oxygen. An evaluation of spontaneous adverse event reporting of MetHba submitted to FDA through 2013 identified 375 reports associated with benzocaine and 16 reports associated with lidocaine. The current study was performed to determine the relative ability of benzocaine and lidocaine to produce methemoglobin (MetHb) in vitro. Incubation of 500muM benzocaine with whole human blood and pooled human liver S9 over 5h resulted in MetHb levels equaling 39.8+/-1.2% of the total hemoglobin. No MetHb formation was detected for 500muM lidocaine under the same conditions. Because liver S9 does not readily form lidocaine hydrolytic metabolites based on xylidine, a primary metabolic pathway, 500muM xylidine was directly incubated with whole blood and S9. Under these conditions MetHb levels of 4.4+/-0.4% were reached by 5h. Studies with recombinant cytochrome P450 revealed benzocaine to be extensively metabolized by CYP 1A2, with 2B6, 2C19, 2D6, and 2E1 also having activity. We conclude that benzocaine produces much more MetHb in in vitro systems than lidocaine or xylidine and that benzocaine should be more likely to cause MetHba in vivo as well.

DrugBank Data that Cites this Article

Drugs
Drug Enzymes
DrugEnzymeKindOrganismPharmacological ActionActions
BenzocaineCytochrome P450 1A2ProteinHumans
Unknown
Substrate
Details
BenzocaineCytochrome P450 2B6ProteinHumans
Unknown
Substrate
Details
BenzocaineCytochrome P450 2C19ProteinHumans
Unknown
Substrate
Details
BenzocaineCytochrome P450 2D6ProteinHumans
Unknown
Substrate
Details
BenzocaineCytochrome P450 2E1ProteinHumans
Unknown
Substrate
Details
Drug Reactions
Reaction
Details
Details
Details