Abstract
Phenobarbital-N-glucoside (PNG) has recently been identified as a significant metabolite of phenobarbital (PB) in man. Glucosidation is an uncommon metabolic pathway for drugs in mammals. Bilirubin is glucosidated as well as glucuronidated. However, few xenobiotics have been recognized to be metabolized through this pathway.
Four neonates treated with PB alone for seizures were studied. Serum concentrations ranged from 30 to 80 mg/l. Serial single daily voided urine specimens were analyzed for PB, PNG, and total p-hydroxyphenobarbital (PHPB). PHPB was first excreted on the 4th day of life in 2 patients and 10th day in 2. No PNG was detected by the 12th day in 1 case or 16th day in 2 cases. In the fourth case, the oldest by estimated gestational age, PHPB was first detected on day 4, and PNG on day 14. On day 20, PNG accounted for 50% of the drug excreted in the urine. Production of PHPB glucuronide was not assessed.
It appears that N-glucosidation is a significant route for PB metabolism in the neonate. This pathway develops rapidly but after aryl hydroxylation.
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Garrettson, L., Bhargava, V. & Soine, W. 365 DEVELOPMENT OF PHENOBARBITAL GLUCOSIDATION IN THE HUMAN NEONATE. Pediatr Res 19, 171 (1985). https://doi.org/10.1203/00006450-198504000-00395
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DOI: https://doi.org/10.1203/00006450-198504000-00395