Administration-time-dependency of the pharmacokinetic behavior and therapeutic effect of a once-a-day theophylline in asthmatic children

M. H. Smolensky, P. H. Scott, R. B. Harrist, P. H. Hiatt, T. K. Wong, J. C. Baenziger, B. J. Klank, A. Marbella, A. Meltzer

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

Using a double-blind, placebo-control, crossover study design, 8 asthmatic children (8-15 years) were evaluated for temporal patterns in airways function throughout separate study periods when treatment was placebo or Theo-24® once-daily on separate occasions at 0600, 1500 or 2100 hr. During 39-hr in-hospital observations, pulmonary function and serum theophylline concentrations (STC) were assessed every 3 hr under all treatments. The pharmacokinetics of Theo-24® varied greatly depending on the dosing time. For the afternoon and evening dosings, the CmaxTmax, AUC1%swing,%fluctuation,%AUC fluctuation,%nocturnal excess and Cav(2,6hr)were all statistically significantly greater than for the morning dosing. Compared with the placebo regimen, dosing patients with Theo-24® at 1500 hr disrupted circadian patterns of airways function, especially airways patency, while dosing at 2100 hr, reduced the amplitude and shifted the acrophase of several spirometric measures to a slightly earlier time. Theo-24® treatment irrespective of dosing time resulted in comparable enhancement of the group24-hr mean, minimum and maximum values of airways patency with reference to placebo baselines. Theo-24® dosing at 1500 or 2100 hr, however, resulted in the best effect on the airways as assessed by the 24-hr mean FEV1.0level in 7 of the 8 asthmatic children. When the drug was given at 1500 hr, the time of lowest FEV1.0was shifted from the nighttime hours in 5 of 8 patients. These Findings suggest that clinicians need to individualize the theophylline dosing schedule of patients to best control the symptoms of asthma.

Original languageEnglish (US)
Pages (from-to)435-447
Number of pages13
JournalChronobiology International
Volume4
Issue number3
DOIs
StatePublished - Jan 1 1987

Keywords

  • Asthma
  • Children
  • Chrono-pharmacology
  • Once-a-day theophylline
  • Pharmacodynamics
  • Pharmacokinetics

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)
  • Agricultural and Biological Sciences (miscellaneous)

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