Comparative study of the pharmacokinetic characteristics of slow release theophylline oral preparations in Thai children with persistent asthma.

Significant differences in the rate and extent of absorption exist between slow release theophylline (SRT) preparations. The pharmacokinetic characteristics of Xanthium were compared with those of Theo-Dur in twelve Thai children with stable persistent asthma by randomized, double blind, crossover study. Serum theophylline concentrations (STCs) were determined by fluorescence polarization immunoassay. The pharmacokinetic parameters were estimated by using a computer program (Topfit 2.0). The STCs, at steady state after different doses, were predicted by using the modified Wagner-Nelson Equation. The mean resident time (MRT) and apparent T1/2 were significantly larger for Xanthium, but the Cmax and AUC0-infinity of Xanthium were significantly lower than those of Theo-Dur. The Frel of Xanthium was 80.1% relative to Theo-Dur. The appropriate dosing interval of both preparations for Thai children was twice a day.

A single-dose comparison of three slow-release theophylline oral preparations in healthy Thai volunteers.

The study was done to compare the pharmacokinetic characteristics of three slow-release theophylline (SRT) preparations. Twelve healthy nonsmokers were randomly assigned a single dose of the following treatments at weekly intervals: Theo-Dur, Theo-24 or Xanthium orally, or aminophylline intravenously. Serially collected serum samples were analyzed for theophylline with use of fluorescence polarization immunoassay (FPIA). All three SRT preparations showed reliable absorption characteristics, but Theo-Dur had a shorter Tmax and MRT and a higher Ka. The pharmacokinetic characteristics of Theo-24 and Xanthium were similar except that Xanthium had lower bioavailability. Using single dose data for simulation of steady state pharmacokinetics, we found that a once-a-day dosage regimen with either Theo-24 or Xanthium would maintain serum levels within the therapeutic range for average non-smoking young adults whereas more frequent dosing intervals with Theo-Dur would be more appropriate. Our results argue against open substitution of SRT preparations without, close monitoring of the serum theophylline concentrations when a change is made.