Prediction of steady-state serum theophylline concentration in children by first-order and zero-order absorption models.
We estimated the pharmacokinetic characteristics of theophylline in children with bronchial asthma after multiple oral dosing of Theo-Dur, in order to determine whether the absorption of the drug is best described by a zero-order absorption kinetic model (0-order model) or a first-order absorption kinetic model (1-order model). Thirteen children with bronchial asthma were evaluated in this study. Each patient received Theo-Dur twice daily at 12-hour intervals. Blood samples were taken at 0, 3, 6, 9 and 12 hours after the administration; plasma theophylline concentration was determined by the fluorescence polarization immuno assay method. Pharmacokinetic parameters for each patient were estimated by a one-compartment open model with 0-order or 1-order absorption and 1-order elimination rate constants. The regression curve predicted using the 0-order model fitted well to the observed value. In contrast, the use of the 1-order model was overestimated considerably in the absorption phase the precision of the prediction using the 0-order model was better than the use of the 1-order model. This study suggests that the 0-order model gave better estimated pharmacokinetic parameters when applied to Theo-Dur than did the 1-order model in children.
Kato
Z
Z
Department of Pediatrics, Gifu University School of Medicine, Japan.
Fukutomi
O
O
Yamazaki
M
M
Kondo
N
N
Imaeda
N
N
Orii
T
T
D000293:Adolescent; D001249:Asthma / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005454:Fluorescence Polarization; D006801:Humans; D007408:Intestinal Absorption; D008297:Male; D008954:Models, Biological; D015203:Reproducibility of Results; D013806:Theophylline / Q000097:blood / Q000493:pharmacokinetics*
D013806:Theophylline