A urinary metabolite ratio that reflects systemic caffeine clearance

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Abstract
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-demthylation products relative to a paraxanthine 8-hydroxylation product (r = 0.91; P < 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 < 0.001) mean metabolite ratio than adults (n = 61), oral contraceptive users (n = 9) had lower (P < 0.05) ratios than women not taking oral contraceptives (n = 30), and smokers (n = 26) had higher (P < 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.

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