Pharmacokinetic comparison of a once-daily and twice-daily theophylline delivery system.
The steady-state pharmacokinetics of a formulation of a 24-hour extended-release theophylline preparation (Uni-Dur) were compared with a twice-daily formulation (Theo-Dur) 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 doses of Theo-Dur) in a randomized, two-way crossover design with no washout period between treatments. Blood samples were collected just before 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 doses 5 of Uni-Dur and doses 9 and 10 of Theo-Dur. The mean serum theophylline concentration-time curves were similar for both formulations from 2 to 18 hours postdose, and the maximum serum theophylline concentrations were comparable (7.66 micrograms/mL for Uni-Dur compared with 7.78 micrograms/mL for Theo-Dur). Fluctuations in serum theophylline concentrations were greater with Uni-Dur (139 +/- 85% compared with 72 +/- 25% normalized to trough serum concentrations; 77 +/- 22% compared with 53 +/- 13% normalized to average steady-state serum concentrations). Based on the area under the curves, the extent of absorption of Uni-Dur was 91.42 +/- 14.24% of Theo-Dur. These findings suggest that the clinical response in patients treated with once-daily Uni-Dur may be equivalent to Theo-Dur given every 12 hours. Furthermore, because of the similar serum concentration over time profiles of the two formulations, it is unlikely that additional monitoring of serum levels during a conversion will be necessary.
González
M A
MA
P'-Kinetics, Inc., Pembroke Pines, Florida.
Kisicki
J
J
Straughn
A B
AB
D000284:Administration, Oral; D000328:Adult; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D004334:Drug Administration Schedule; D006207:Half-Life; D006801:Humans; D007408:Intestinal Absorption; D008297:Male; D013806:Theophylline / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*
D003692:Delayed-Action Preparations; D013806:Theophylline