Ontogeny of dextromethorphan O- and N-demethylation in the first year of life.
Clin Pharmacol Ther
; 81(4): 510-6, 2007 Apr.
Article
in En
| MEDLINE
| ID: mdl-17301735
ABSTRACT
The exponential increase in the number of drugs used to treat infant and childhood illnesses necessitates an understanding of the ontogeny of drug biotransformation for the development of safe and effective therapies. Healthy infants received an oral dose (0.3 mg/kg) of dextromethorphan (DM) at 0.5, 1, 2, 4, 6, and 12 months of age. DM and its major metabolites were measured in urine. CYP2D6 genotype was determined by polymerase chain reaction-restriction fragment length polymorphism. Genotyping data indicated a strong correlation between CYP2D6 genotype and DM O-demethylation (beta=-0.638; 95% CI -0.745, -0.532; P<0.001). CYP2D6 activity was detectable and concordant with genotype by 2 weeks of age, showed no relationship with gestational age, and did not change with post natal age up to 1 year. In contrast, DM N-demethylation developed significantly more slowly over the first year of life. Genotype and the temporal acquisition of drug biotransformation are critical determinants of a drug response in infants.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Antitussive Agents
/
Aging
/
Dextromethorphan
Limits:
Female
/
Humans
/
Infant
/
Male
/
Newborn
Language:
En
Journal:
Clin Pharmacol Ther
Year:
2007
Document type:
Article
Affiliation country:
United States