¹Children's Mercy Hospitals and Clinics, Kansas City, MO

Abstract

Background/aims: Dietary constituents alter drug metabolism in adults contributing to therapeutic failure or toxicity. The effect of diet on drug disposition in infants was investigated in this study.

Methods: Oral caffeine (CAF) and dextromethorphan (DEX) were given to 35 healthy infants at 6 visits over their first 6 months of life. CAF was measured in plasma to determine the apparent elimination rate constant (k_e). CAF, DEX, and their metabolites were measured by HPLC in urine samples collected over 24 hr.

Results: CAF k_e at the first visit (2 wks) was low and unrelated to post-conceptional age. After 2 wks, CAF k_e displayed a significant positive linear correlation with post-natal age (k_e = .004 (Age[wks]) + .001; p<0.001). CAF k_e increased faster in formula-fed infants (slope = 0.005 95%CI: 0.004, 0.006) than in breast-fed infants (slope = 0.002 95%CI: 0.001, 0.002) (p<0.001). CAF k_e in formula-fed infants was associated with increased conversion of CAF to 3-demethylated metabolites. DEX metabolism, assessed as the fractional molar recovery of 3-hydroxymorphinan (fr3HM), showed a similar marked increase with postnatal age[(fr3HM) = .014 Age[wks] + .203; p< 0.001] that did not differ between diets.

Conclusions: Formula feeding accelerates the development of CAF metabolism but not DEX. Components of an infant's diet differentially modify the developmental regulation of drug metabolizing enzymes. Dietary modification of drug metabolism appears to alter exposure to xenobiotics from a very early age.