Clearance and metabolism of mepivacaine in the human neonate

The metabolism of mepivacaine in the human neonate and adult has been examined. Three types of metabolic reaction are involved in the adult: N‐demethylation to produce 2′,6′‐pipecoloxylidide, aromatic hydroxylations to produce 2′,6′‐pipecoloxylidide‐4′‐hydroxy‐1‐methyl and 2′,6′‐pipecoloxylidide‐3′‐hydroxy‐1‐methyl, both of which undergo glucuronide conjugation. More than 99 per cent of each phenol is excreted as a glucuronide. Excretion of mepivacaine is influenced by urinary pH, 10 per cent of the dose being excreted by subiects with acidified urine and 5 per cent by subjects with fluctuating urinary pH. Urine passed in the first 30 hours of life of neonates whose mothers had received mepivacaine during labor was examined for mepivacaine and metabolites. The results show that there is considerable net transfer of mepivacaine to the fetus as indicated by the urinary excretion of mepivacaine and metabolites. Aromatic hydroxylation does not occur, or if it does it is so inefficient as to be of no clinical significance. The position with N‐demethylation is not so clear as the data does not provide adequate evidence on which to make a clear decision. Even though the neonate either has a very limited capacity to metabolize mepivacaine or is incapable of doing so, it is still able to eliminate the drug. Approximately 90 per cent of the total amount of mepivacaine found in the urine of neonates was excreted in the first 24 hoors after delivery.