High levels of methylxanthines in chocolate do not alter theobromine disposition

Theobromine disposition was measured twice in 12 normal men, once after 14 days of abstention from all methylxanthines and once after 1 week of theobromine (6 mg/kg/day) in the form of dark chocolate. Mean theobromine t½, apparent volume of distribution, and clearance after abstinence from all methylxanthines were 10.0 hours, 0.76 L/kg, and 0.88 ml/min/kg. High daily doses of chocolate for 1 week did not change these values. After subjects abstained from methylxanthines, urinary radioactivity over 72 hours after a single, oral dose of [8‐ 14 C]theobromine consisted of 42% 7‐methylxanthine, 20% 3‐methylxanthine, 18% theobromine, 10% 7‐methyluric acid, and 10% 6‐amino‐5[ N methyl‐formylamino]‐1‐methyluracil. A week of daily theobromine consumption in the form of dark chocolate also did not alter this urinary profile of theobromine and its metabolites. Although these results might appear to differ from other reports of inhibition of theobromine elimination after five consecutive daily doses of theobromine in aqueous suspensions, both the rate and extent of absorption of theobromine in chocolate were less then that of theobromine in solution. Relative bioavailability of theobromine in chocolate was 80% that of theobromine in solution. This reinforces the fundamental principle that both the metabolic and the therapeutic consequences of a particular chemical can differ when that chemical is given in the pure compared with the dietary form. Clinical Pharmacology and Therapeutics (1985) 37, 415–424; doi: 10.1038/clpt.1985.65