Studies on theobromine disposition in normal subjects; Alterations induced by dietary abstention from or exposure to methylxanthines

Abstract

Normal male volunteers on xanthine-restricted diets had a plasma theobromine (TB) half-life (t^½) of6.1 ± 0.7 hr (mean ± SEM), a TB metabolic clearance rate (MCR) of 113.8 ± 6.8 mllmin (mean ± SEM). and an apparent volume of distribution (aVd) of 59.9 ± 7.8 L (mean ± SEM) after a single oral dose of6 mg/kg of TB. A two-week period of dietary abstention from methylxanthines shortened the mean plasma TB t^½ by 33% and increased the mean MCR ofTB by 59%; no change occurred in mean aVd of TB. In another experiment, normal male volunteers received the same oral dose of TB for each of five consecutive days. The mean plasma TB t^½ measured immediately after the last TB dose was prolonged by almost two-thirds, while the mean aVd increased 23%. Although the mean plasma TB t^½ measured four days after this last TB dose was the same as that measured after a single oral dose, the mean MCR of TB increased by 34%, but this change was balanced by increased mean aVd of 35%. These results suggest that immediately after five daily doses ofTB, an impairment ofTB clearance occurs that is reversible by four days of dietary abstention from methylxanthines.