Caffeine metabolism in liver slices during postnatal development in rats.
The metabolism of caffeine was investigated in liver slices from newborn, preweanling, postweanling, and adult rats. All metabolites were identified and quantified by HPLC without using radioactive compound. Caffeine metabolism underwent dramatic changes during maturation in rats. The specific activity of the enzyme system was extremely low when liver slices from 1-day and 7-day-old rats were used. This capacity increased gradually with increasing age and reached a peak following weaning at 21 days of age. In rat liver slices, N-1 demethylation to theobromine was the main pathway of in vitro caffeine metabolism at all ages. Theobromine represented 25% of total caffeine metabolites at day 1 and about 40% at all others ages. 1,3,7-6-amino-5-(N-formylmethylamino)-1,3-dimethyluracil is a minor metabolite in newborn (1-day-old), preweanling (7-day-old), and adult rats (120-day-old), but an important metabolite in postweanling rats. Conversely, 1,3,7-trimethyluric acid is a major metabolite in newborn and adult rats and a minor one in preweanling and postweanling rats. This liver slices model could be used as a simple and versatile model to study metabolism during maturation.
Bienvenu
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T
Département de Pharmacologie Périnatale et Pédiatrique, Hôpital Saint Vincent de Paul, Paris, France.
Pons
G
G
Rey
E
E
Thiroux
G
G
Olive
G
G
D000818:Animals; D001711:Biotransformation; D002110:Caffeine / Q000378:metabolism* / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid; D008099:Liver / Q000033:anatomy & histology / Q000254:growth & development* / Q000378:metabolism*; D008297:Male; D008745:Methylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013805:Theobromine / Q000378:metabolism / Q000493:pharmacokinetics; D013806:Theophylline / Q000378:metabolism / Q000493:pharmacokinetics; D014498:Uracil / Q000031:analogs & derivatives / Q000096:biosynthesis
C029567:6-amino-5-(formyl-N-methylamino)-1,3-dimethyluracil; D002110:Caffeine; D014498:Uracil; D013806:Theophylline; D013805:Theobromine; C021183:1,7-dimethylxanthine