A urinary metabolite ratio that reflects systemic caffeine clearance.
Systemic caffeine clearance and urinary metabolite profiles were determined in 15 subjects with diverse exposure histories to cytochrome P-450 inducers (cigarette smoke) and inhibitors (oral contraceptive steroids). A correlation was observed between caffeine clearance and a urinary ratio based on the molar recovery of paraxanthine 7-demethylation products relative to a paraxanthine 8-hydroxylation product (r = 0.91; P less than 0.001). Analysis of urinary metabolites was undertaken in a larger population to assess the effects of gender, age, oral contraceptives, and smoking on the ratio. No gender differences were observed in either adults or children; children (n = 21) showed a higher (P less than 0.001) mean metabolite ratio than adults (n = 61), oral contraceptive users (n = 9) had lower (P less than 0.05) ratios than women not taking oral contraceptives (n = 30), and smokers (n = 26) had higher (P less than 0.001) ratios than nonsmokers (n = 61). The data indicate that a urinary metabolite ratio based on paraxanthine 7-demethylation/8-hydroxylation products reflects systemic caffeine clearance and likely monitors cytochrome P-450 activity inducible by polycyclic aromatic hydrocarbons.
D000328:Adult; D000367:Age Factors; D044466:Asian People; D002110:Caffeine / Q000378:metabolism* / Q000652:urine; D002648:Child; D002675:Child, Preschool; D003276:Contraceptives, Oral / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D005260:Female; D006801:Humans; D007700:Kinetics; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D012907:Smoking; D013997:Time Factors; D014498:Uracil / Q000031:analogs & derivatives / Q000652:urine; D014527:Uric Acid / Q000031:analogs & derivatives / Q000652:urine; D044465:White People; D014970:Xanthines / Q000652:urine
D003276:Contraceptives, Oral; D014970:Xanthines; D014527:Uric Acid; C030530:1-methyluric acid; D002110:Caffeine; D014498:Uracil; C053085:1-methylxanthine; C036692:5-acetylamino-6-formylamino-3-methyluracil; D003577:Cytochrome P-450 Enzyme System; C053084:1,7-dimethyluric acid