Biotransformation of caffeine in human liver microsomes from foetuses, neonates, infants and adults

Br J Clin Pharmacol. 1994 May;37(5):405-12. doi: 10.1111/j.1365-2125.1994.tb05706.x.


1. Caffeine metabolism was studied in human liver microsomes from foetuses (n = 10), neonates (n = 10), infants (n = 9) and adults (n = 5). Caffeine and its metabolites, 1-3-7-trimethyluric acid, paraxanthine, theophylline and theobromine, were assayed by h.p.l.c. Methoxyresorufin-O-demethylase activity (MEROD) was determined and immunoquantifiable levels of CYP1A2 were measured. 2. The formation of the dimethylxanthines by N-3, N-7 or N-1-demethylation was significantly less in foetuses, neonates and infants than in adults, as shown previously in vivo. The formation of 1-3-7-trimethyluric acid (C-8-hydroxylation) was not significantly different between age groups. The production of total dimethylxanthines, paraxanthine and theophylline increased significantly with age within the neonate-infant group over at least the 0-300 day range (rs = 0.739, 0.667, 0.682, respectively). These data differ from those reported in vivo which suggested that N-3 and N-7-demethylations matured at about 120 days. The difference in maturational profiles of each metabolic pathway suggests that the reactions depend on different isoenzymes. The delay in the maturation of N-1 compared with N-3 and N-7-demethylation is in agreement with previous in vivo data. 3. In the neonate-infant group, only N-3-demethylation correlated with both MEROD activity (rs = 0.681; P < 0.05) and CYP1A2 microsomal concentration (rs = 0.454; P approximately 0.05), suggesting that, as in adults, this reaction depends on CYP1A2. 4. In the foetal samples, the production of total dimethylxanthines, paraxanthine and theobromine decreased significantly (rs = -0.879, -0.767, -0.708, respectively) with increasing gestational age.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Aging / metabolism*
  • Biotransformation
  • Caffeine / metabolism*
  • Caffeine / pharmacokinetics
  • Chromatography, High Pressure Liquid
  • Cytochrome P-450 CYP1A2
  • Cytochrome P-450 Enzyme System / metabolism
  • Female
  • Fetus / metabolism*
  • Gestational Age
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Microsomes, Liver / enzymology
  • Microsomes, Liver / metabolism*
  • Oxidoreductases / metabolism


  • Caffeine
  • Cytochrome P-450 Enzyme System
  • Oxidoreductases
  • methoxyresorufin-O-demethylase
  • Cytochrome P-450 CYP1A2