Theophylline dose-concentration relationship of a 12-hourly Nuelin SA regimen supplemented with nocturnal nuelin liquid in healthy volunteers.
Twelve healthy male volunteers who were diurnally active between 05:00 and 23:00 took part in a randomized, multiple-dose, double-blind, four-way, crossover study to determine the relationship between the dose of a nonsustained-release theophylline (NSRT) formulation added to the evening administration of a 12-hourly sustained-release theophylline (SRT) regimen and the elevation of the early morning (between 02:00 and 05:00) steady-state plasma theophylline concentration. The four treatments were 250 mg Nuelin SA (sustained-release theophylline) every 12 h plus either placebo or Nuelin liquid (non-sustained-release theophylline) equivalent to 100 mg, 200 mg, or 300 mg of theophylline. Without evening supplementation (placebo), the early morning plasma theophylline concentrations were 13% lower than the average 24-h concentration, but with evening supplementation the early morning plasma theophylline concentration could be raised up to and above the average 24-h concentration. A prediction equation for the early morning plasma theophylline concentration as a function of the additional evening dose of Nuelin liquid, and of the steady-state evening trough plasma theophylline concentration without evening supplementation, was established. This prediction equation can be used to determine the additional evening dose of Nuelin liquid (administered at 19:00) needed to reduce early morning bronchoconstriction in asthmatic patients who are on a 12-hourly Nuelin SA (drug administered at 07:00 and 19:00) regimen.
Schall
R
R
Department of Pharmacology, University of the Orange Free State, Bloemfontein, South Africa.
Middle
M V
MV
Müller
F O
FO
du Plessis
J B
JB
D000328:Adult; D002940:Circadian Rhythm; D003692:Delayed-Action Preparations; D004311:Double-Blind Method; D006801:Humans; D008297:Male; D012044:Regression Analysis; D013806:Theophylline / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*
D003692:Delayed-Action Preparations; D013806:Theophylline