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• W2038091811 abstract "Objectives A number of caffeine metabolite ratios have been proposed to measure CYP1A2 activity in vivo. The data to validate these ratios are scanty. The objective of this study was to validate urine caffeine metabolite ratios versus stable isotope-labeled caffeine clearance under different caffeine dosing conditions. Study design Two experiments, one with nine nonsmoking subjects and the other with 12 cigarette smokers, were performed. We explored the relationship between caffeine clearance, measured by means of intravenous infusions of stable isotope-labeled caffeine, and a number of caffeine metabolite ratios during administration of different single or multiple doses doses of caffeine to smokers and nonsmokers on three different occasions over a 2-week period, using different durations of urine collections, including spot urines. The stable isotope technique allowed simultaneous oral dosing of caffeine and measurement of caffeine metabolite ratios and caffeine clearance, the latter reflecting CYP1A2 activity. Results The caffeine metabolite ratio of AAMU+1U+1X/17U (5-acetylamino-6-amino-3-methyluracil + 1-methyluric acid + 1 methylxanthine/1,7-dimethyluric acid) maintained a significant correlation with caffeine clearance for all the above conditions (r2 range, 0.4 to 0.9) except for dose. With high doses of caffeine (12 mg/kg), a significant relationship was not observed. AAMU+1U+1X/17U also correlated with the formation clearance of paraxanthine (r2 = 0.6, p = 0.002). Other reported caffeine metabolite ratios did not display the same robust correlation with caffeine clearance under all these different conditions. Conclusions We conclude that AAMU+1U+1X/17U measured from a single spot urine collection is a valid measure of CYP1A2 activity except at very high levels of caffeine dosing. The validity of the other proposed caffeine metabolite ratios is questionable. Clinical Pharmacology & Therapeutics (1996) 59, 284–296; doi:" @default.
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• W2038091811 date "1996-03-01" @default.
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• W2038091811 title "Validation of urine caffeine metabolite ratios with use of stable isotope-labeled caffeine clearance*" @default.
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• W2038091811 doi "https://doi.org/10.1016/s0009-9236(96)80006-3" @default.
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