Biotransformation of caffeine in human liver microsomes from foetuses, neonates, infants and adults
Cazeneuve, C; Pons, G; Rey, E; Treluyer, J; Cresteil, T; Thiroux, G; D'Athis, P; Olive, G
HERO ID
699807
Reference Type
Journal Article
Year
1994
Language
English
PMID
| HERO ID | 699807 |
|---|---|
| In Press | No |
| Year | 1994 |
| Title | Biotransformation of caffeine in human liver microsomes from foetuses, neonates, infants and adults |
| Authors | Cazeneuve, C; Pons, G; Rey, E; Treluyer, J; Cresteil, T; Thiroux, G; D'Athis, P; Olive, G |
| Journal | British Journal of Clinical Pharmacology |
| Volume | 37 |
| Issue | 5 |
| Page Numbers | 405-412 |
| Abstract | 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) |
| Pmid | 8054245 |
| Wosid | WOS:A1994NK53900002 |
| Is Certified Translation | No |
| Dupe Override | No |
| Is Public | Yes |
| Language Text | English |
| Keyword | CAFFEINE METABOLISM; HUMAN MICROSOMES; MATURATION |
| Relationship(s) |
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