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 < 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. Clinical Pharmacology and Therapeutics (1987) 42, 157–165; doi: 10.1038/clpt.1987.126