PHARMACOKINETIC COMPARISON OF A ONCE-DAILY AND TWICE-DAILY THEOPHYLLINE DELIVERY SYSTEM

The steady-state pharmacokinetics of a formulation of a 24-hour extend ed-release theophylline preparation (Uni-Dur(R)) were compared with a twice-daily formulation (Theo-Dur(R)) in healthy volunteers. Eighteen healthy, adult, male volunteers received both treatments (600-mg dose of Uni-Dur every morning for 5 doses or 300 mg every 12 hours for 10 d oses of Theo-Dur) in a randomized, two-way crossover design with no wa shout period between treatments. Blood samples were collected just bef ore doses 3, 4, and 5 of Uni-Dur and before doses 5, 7, and 9 of Theo- Dur, as well as at 2-hour intervals for 24 hours following dose 5 of U ni-Dur and doses 9 and 10 of Theo-Dur. The mean serum theophylline con centration-time curves were similar for both formulations from 2 to 18 hours postdose, and the maximum serum theophylline concentrations wer e comparable (7.66 mug/mL for Uni-Dur compared with 7.78 mug/mL for Th eo-Dur). Fluctuations in serum theophylline concentrations were greate r with Uni-Dur (139 +/- 85% compared with 72 +/- 25% normalized to tro ugh serum concentrations; 77 +/- 22% compared with 53 +/- 13% normaliz ed to average steady-state serum concentrations). Based on the area un der the curves, the extent of absorption of Uni-Dur was 91.42 +/- 14.2 4% of Theo-Dur. These findings suggest that the clinical response in p atients treated with once-daily Uni-Dur may be equivalent to Theo-Dur given every 12 hours. Furthermore, because of the similar serum concen tration over time profiles of the two formulations, it is unlikely tha t additional monitoring of serum levels during a conversion will be ne cessary.