title: Theophylline levels after single daily and divided dosing of a once-a-day theophylline preparation in asthmatic children.
abstract: Twelve children with chronic asthma were treated with a single dose of sustained-release theophylline once-a-day taken after supper at 9 PM. During the steady-state period after 15 days of treatment, serum theophylline levels were measured one and two hours after dosing and then every two hours until 9 PM the following day. The peak concentration (mean +/- SD) of serum theophylline (20.9 +/- 6.5 micrograms/mL) was observed eight hours after dosing while the through concentration (4.34 +/- 2.62 micrograms/mL) was measured 24 hours after dosing; the percent fluctuation (mean +/- SD) was 966.45 +/- 1105.55%. Another 15 children were treated with the same preparation administered at 8 AM after breakfast and at 8 PM after supper. Serum samples for theophylline concentration were obtained immediately before dosing at 8 AM and then every two hours for the following 12 hours. The mean theophylline level observed immediately before dosing at 8 AM was 10.16 +/- 3.84 micrograms/mL while the mean level at 8 PM was 9.39 +/- 4.77 micrograms/mL. The peak serum level was 13.07 +/- 5.13 micrograms/mL at 2 PM, while the trough was 9.31 +/- 3.71 micrograms/mL at 10 AM, with a percent fluctuation of 155.21 +/- 147.95%. Few side effects were seen in both groups. The results of our study clearly demonstrated that in children the percent fluctuation and peak-trough differences are far greater with once daily than with twice daily dosing and this should be considered when planning theophylline treatment in asthmatic children. The administration of a once-a-day preparation every 8-12 hours can however result in overlapping absorption patterns.
authors.affiliation: Clinica Pediatrica, Universita di Verona, Italy.
authors.forename: A L
authors.initials: AL
authors.lastname: Boner
authors.forename: L
authors.initials: L
authors.lastname: Sette
authors.forename: G
authors.initials: G
authors.lastname: Vallone
authors.forename: M
authors.initials: M
authors.lastname: Plebani
authors.forename: A
authors.initials: A
authors.lastname: Messori
mesh_terms: D000293:Adolescent; D001249:Asthma / Q000188:drug therapy*; D001682:Biological Availability; D002648:Child; D002940:Circadian Rhythm; D003692:Delayed-Action Preparations; D005260:Female; D006801:Humans; D008297:Male; D013806:Theophylline / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics
chemical_list: D003692:Delayed-Action Preparations; D013806:Theophylline