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A urinary metabolite ratio that reflects systemic caffeine clearance
Author(s) -
Campbell Monica E,
Spielberg Stephen P,
Kalow Werner
Publication year - 1987
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1987.126
Subject(s) - paraxanthine , metabolite , caffeine , chemistry , urinary system , pharmacology , hydroxylation , medicine , physiology , endocrinology , cyp1a2 , cytochrome p450 , metabolism , biochemistry , enzyme
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