{'fraction_non_alphanumeric': 0.03392967304133251, 'fraction_numerical': 0.0351634793337446, 'mean_word_length': 4.772241992882562, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 1, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Surge in expression of carboxylesterase 1 during the post-neonatal stage enables a rapid gain of the capacity to activate the anti-influenza prodrug oseltamivir.

BACKGROUND
Oseltamivir, a widely used anti-influenza drug, is hydrolytically activated by carboxylesterase 1 (CES1). The expression of this carboxylesterase is developmentally regulated. This study was performed to determine when after birth infants acquire competence of activating this prodrug.


METHODS
Liver tissue samples were collected and divided into 5 age groups: group 1 (1-31 d old), group 2 (35-70 d old), group 3 (89-119 d old), group 4 (123-198 d old), and group 5 (>18 years of age). These samples were analyzed for oseltamivir hydrolysis and CES1 expression.


RESULTS
Liver samples in group 1 expressed the lowest level of CES1 with the lowest hydrolytic activity toward oseltamivir. A 4-7-fold increase between groups 1 and 2 (1-31 vs 35-70 d of age) was detected in the hydrolysis and expression analyses, respectively. Liver samples in the other 3 pediatric groups (35-198 d of age) exhibited similar expression and hydrolysis levels. Overall, liver samples in group 1 had CES1 expression and hydrolysis levels that were 10% of those of adults, whereas liver samples in the other 3 pediatric groups had levels that were ∼50% of adult levels.


CONCLUSIONS
The post-neonatal surge in CES1 expression ensures the hydrolytic capacity to be gained rapidly after birth in infants, but the larger variability during this period suggests that caution should be exercised on the extrapolated dosing regimens of ester drugs from other age groups.