Determination of theophylline bioavailability using saliva theophylline concentrations

Substantial error occurs when individual saliva theophylline concentrations are used to predict serum theophylline concentrations. However, the use of saliva theophylline concentrations to determine product bioavailability has never been evaluated. Subjects in this study were 18 stable patients (20–51 yr) with a history of chronic obstructive pulmonary disease. Three preparations — a capsule (Elixophyllin 400 mg), elixir (Elixophyllin 373 mg), and tablet (Theolair 375 mg) — were administered in a randomized crossover design. Serum and saliva samples were obtained pre‐dose and 0.25, 0.5, 1, 2, 4, 6, and 8 hours after theophylline administration. The saliva AUC_0–∞ and serum AUC_0–∞ were highly associated for the elixir (r = 0.84) tablet (r = 0.89), and capsule (r = 0.89). The bioavailability of the tablet and capsule calculated from elixir saliva and elixir serum AUC_0–∞ were not significantly different (p = 0.2). The bioavailability of the tablet calculated from saliva and serum was 93% and 102%, respectively. The bioavailability of the capsule calculated from saliva and serum was 113% and 102% respectively. Our data suggests that theophylline bioavailability can be reliably estimated from saliva theophylline concentrations. However, study designs that include larger sample sizes and more frequent sampling may be necessary when determining bioavailability from saliva. 1983 Pharmacotherapy Publications Inc.