I. Kinetics and metabolism of theobromine in male rats

M. Bonati, R. Latini, B. Sadurska, E. Riva, F. Galletti, J. F. Borzelleca, S. M. Tarka, M. J. Arnaud, S. Garattini

Research output: Contribution to journalArticle

Abstract

On the basis of general pharmacological information (blood cells/plasma partition, plasma protein binding) and using HPLC as the principal analytical method, we investigated the kinetics and metabolism of theobromine (a caffeine metabolite) in male rats after a single dose and after a 2 week chronic application. Doses in both conditions varied between 1 and 100 mg/kg. In in vitro and in vivo the fraction of theobromine unbound to plasma proteins averaged 0.90 over a wide range of concentrations. No significant difference was found in the pharmacokinetic profile of the drug after acute or chronic treatment at different doses except for a reduction in the absorption rate constant as the dose increased. AUC values increased in proportion to the dose. The 2 treatment schedules were also similar as regards metabolism, at least 50% of the administered dose of theobromine being excreted unchanged, and 25% as 6-amino-5-[N-methyl-formylamino]1-methyluracil. Only at the highest doses was there a tendency for theobromine to accumulate at the expense of its major metabolite (a uracil compound).

Original languageEnglish
Pages (from-to)327-341
Number of pages15
JournalToxicology
Volume30
Issue number4
DOIs
Publication statusPublished - Apr 16 1984

Keywords

  • Metabolism
  • Pharmacokinetics
  • Rats
  • Theobromine

ASJC Scopus subject areas

  • Toxicology

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    Bonati, M., Latini, R., Sadurska, B., Riva, E., Galletti, F., Borzelleca, J. F., Tarka, S. M., Arnaud, M. J., & Garattini, S. (1984). I. Kinetics and metabolism of theobromine in male rats. Toxicology, 30(4), 327-341. https://doi.org/10.1016/0300-483X(84)90143-4