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

Normal male volunteers on xanthine-restricted diets had a plasma theobromine (TB) half-life (t1/2) of 6.1 +/- 0.7 hr (mean +/- SEM), a TB metabolic clearance rate (MCR) of 113.8 +/- 6.8 ml/min (mean +/- SEM), and an apparent volume of distribution (aVd) of 59.9 +/- 7.8 L (mean +/- SEM) after a single oral dose of 6 mg/kg of TB. A two-week period of dietary abstention from methylxanthines shortened the mean plasma TB t1/2 by 33% and increased the mean MCR of TB 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 t1/2 measured immediately after the last TB dose was prolonged by almost two-thirds, while the mean aVd increased 23%. Although the mean plasma TB t1/2 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 of TB, an impairment of TB clearance occurs that is reversible by four days of dietary abstention from methylxanthines.