Comparison of caffeine metabolism by slices, microsomes and hepatocyte cultures from adult human liver.
1. Caffeine was used as a molecular probe for hepatic monooxygenase activity in three in vitro models from human livers: slices, microsomes and hepatocyte cultures. 2. A h.p.l.c. method for determination of all possible metabolites of caffeine (16 compounds) is described. 3. Caffeine biotransformation by these three in vitro systems was low. However, metabolite formation was shown to proceed at a rate close to that calculated from in vivo caffeine elimination half-life. 4. Metabolic profiles were the same whatever the in vitro system used. The ratio of primary demethylated metabolites was similar to that measured by in vivo studies, i.e. the selectivity for caffeine N-3 demethylation to paraxanthine was retained. 5. Significant correlation (p less than 0.001) between 7-ethoxyresorufin O-deethylation and caffeine demethylations was demonstrated for the 12 human livers studied.
Berthou
F
F
Laboratoire de biochimie, Faculté de Médecine de Brest, France.
Ratanasavanh
D
D
Riche
C
C
Picart
D
D
Voirin
T
T
Guillouzo
A
A
D000293:Adolescent; D000328:Adult; D001711:Biotransformation; D002110:Caffeine / Q000302:isolation & purification / Q000493:pharmacokinetics*; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D003580:Cytochromes / Q000378:metabolism; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007231:Infant, Newborn; D008099:Liver / Q000378:metabolism*; D008297:Male; D008862:Microsomes, Liver / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000378:metabolism; D010088:Oxidoreductases / Q000378:metabolism; D010105:Oxygenases / Q000378:metabolism
D003580:Cytochromes; D002110:Caffeine; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D010088:Oxidoreductases; D010105:Oxygenases; C017170:Cyp1a2 protein, rat; D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2