A urinary metabolite ratio that reflects systemic caffeine clearance

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-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.

Polymorphisms for Aromatic Amine Metabolism in Humans: Relevance for Human Carcinogenesis

“…In order to select a urinary ratio that accurately reflects caffeine 3-demethylation (and aromatic amine N-oxidation), a pharmacokinetic study was carried out in 12 individuals in whom the levels of caffeine and 15 of its metabolites in blood and urine were measured over a 48-hr period after caffeine dosing (3 mg/ kg). The results indicated that the urinary ratio of [1,7- (37,38).…”

Immunohistochemical detection of pulmonary cytochrome P450IA and metabolic activities associated with P450IA1 and P450IA2 isozymes in lung cancer patients.

“…2B). These results demonstrate the inducing effect of tobacco smoke on P450IA1 in the lung and on P450IA2 probably in the liver of smokers (4,12). Further molecular analyses are required to determine whether CYP1A2 and other CYPs are expressed in the lungs of smokers.…”

HPLC determination of caffeine and paraxanthine in urine: An assay for cytochrome P450 1A2 activity

“…Apiaceous vegetables (dill weed, celery, parsley, parsnip, carrot) have an inhibitory affect while allium vegetables (garlic, onions, scallions, leeks, and chives) have no effect on P450 1A2 activity when compared with a control diet lacking vegetables [18]. Oral contraceptives and estrogen hormone replacement therapy have also been identified as inhibitors of the metabolic activity of P450 1A2 [11,15,19]. Individuals who are exposed to enzyme inducers or inhibitors in the workplace, such as anesthesiologists exposed to anesthetic chemicals in the operating room, gasoline station attendants exposed to high levels of petroleum, and greenhouse workers exposed to pesticides, may also exhibit altered P450 1A2 metabolic activity [20][21][22][23].…”

“…Individuals who are exposed to enzyme inducers or inhibitors in the workplace, such as anesthesiologists exposed to anesthetic chemicals in the operating room, gasoline station attendants exposed to high levels of petroleum, and greenhouse workers exposed to pesticides, may also exhibit altered P450 1A2 metabolic activity [20][21][22][23]. Beyond these environmental factors, age and gender have also been shown to affect P450 1A2 metabolic activity with children having higher activity than adults, and men having higher activity than women, though this latter observation is disputed [11,14,15,18,19].…”

“…Polycyclic aromatic hydrocarbons, also present in high concentrations in charbroiled meats as well as tobacco smoke, serve both as substrates for and inducers of P450 1A2 activity [9]. Thus, individuals with diets high in char-grilled meat and/or are smokers have been shown to have increased P450 1A2 activity [9][10][11][12][13][14][15].…”