Caffeine disposition after oral doses

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Abstract
Caffeine (TMX) disposition was studied in men after 1, 5, and 10 mg/kg in water, as mocha coffee (1.54 mg/kg) and as a soft drink (0.22 mg/kg). TMX and its metabolites were analyzed in plasma and urine by high‐pressure liquid chromatography. The design permitted confirmation of most of the partial results in various experimental settings and contributed new data on the metabolic disposition of TMX, with specific reference to the main dimethylxanthine metabolite found in plasma, paraxanthine (1,7‐dimethylxanthine). Different analysis methods were compared for the calculated parameters (absorption and elimination rate constants and renal clearance) to assess the consistency of results. The kinetics of TMX and of its dimethylated metabolites in plasma were described with a model that used an analogdigital hybrid computing system. In addition to providing a comprehensive profile of TMX disposition in the healthy adult, the results indicate that TMX exhibits dose‐independent kinetics at the levels at which man normally takes TMX. Clinical Pharmacology and Therapeutics (1982) 32, 98–106; doi:10.1038/clpt.1982.132