Caffeine and Its Dimethylxanthine Metabolites in Two Cases of Caffeine Overdose: A Cause of Falsely Elevated Theophylline Concentrations in Serum*

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Abstract
Two children ingested over-the-counter medications containing caffeine, resulting in significant caffeine overdose. Measured concentrations of caffeine were as high as 176 end 128 mg/L. We have described the elimination of caffeine and its dimethylxenthine metabolites, paraxanthine, theophylline, and theobromine in these cases. The apparent theophylline concentrations determined after caffeine ingestion were dependent upon the method of measurement. Use of one published reversed-phase HPLC method, which does not separate theophylline from paraxanthine, resulted in overestimation of theophylline by 225 to 513%. Use of an enzyme immunoassay procedure resulted in a lesser degree of overestimation (142–383%), which was due, in part, to cross-reactivity with extremely high concentrations of caffeine and paraxanthine. The measurement of caffeine concentrations in the management of caffeine overdose is of limited clinical usefulness; likewise, measurement of theophylline concentrations is generally not indicated, and may be misleading unless a highly specific assay is used.

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