Benzyl alcohol metabolism and elimination in neonates.
Reports on fatal benzyl alcohol poisoning in premature neonates implied that the toxicity may be due to larger doses per kilogram than for adults. It has been postulated that the load of benzoic acid (metabolite of benzyl alcohol) may exceed the capacity of the immature liver or kidney for detoxification through glycine conjugation to form hippuric acid. To test this hypothesis, 14 term and 9 preterm neonates receiving loading doses of phenobarbital containing benzyl alcohol were studied. Urine and serum benzoic and hippuric acid levels were measured by GC and HPLC methods, respectively. There was greater accumulation of benzoic acid in the serum of preterm compared to the term neonates which was reflected in higher normalized peak levels (2130.6 vs. 237.8 kg/l, p less than 0.001) and larger normalized AUCIV (1,253.2 vs. 483.0 kg.h/l, p less than 0.01). Furthermore, larger percentages of benzyl alcohol doses were found in urine as benzoic acid in preterm babies, while less hippuric acid appeared in their urine than term newborns. These results indicate that hippuric acid formation is deficient in preterm neonates. Although we did not encounter in our patients the specific toxic signs described as part of the benzyl alcohol toxicity syndrome, we cannot directly answer the issue of safety of 'low doses' of benzyl alcohol as found in some medications administered to neonates. This study confirms the immaturity of the benzoic acid detoxification process in premature newborns.
LeBel
M
M
Ecole de Pharmacie, Université Laval, Ste-Foy, Québec, Canada.
Ferron
L
L
Masson
M
M
Pichette
J
J
Carrier
C
C
D001565:Benzoates / Q000378:metabolism; D019817:Benzoic Acid; D001592:Benzyl Alcohols / Q000493:pharmacokinetics* / Q000652:urine; D001593:Benzyl Compounds / Q000493:pharmacokinetics*; D005260:Female; D006207:Half-Life; D006626:Hippurates / Q000378:metabolism; D006801:Humans; D007231:Infant, Newborn / Q000378:metabolism*; D007234:Infant, Premature / Q000378:metabolism; D008297:Male
D001565:Benzoates; D001592:Benzyl Alcohols; D001593:Benzyl Compounds; D006626:Hippurates; D019817:Benzoic Acid; C030514:hippuric acid