Kinetics and metabolism of theobromine in male rats.
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).
D000818:Animals; D001682:Biological Availability; D001798:Blood Proteins / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D007700:Kinetics; D008297:Male; D011485:Protein Binding; D051381:Rats; D011919:Rats, Inbred Strains; D013805:Theobromine / Q000378:metabolism*
D001798:Blood Proteins; D013805:Theobromine