Abstract
The pharmacokinetics of theophylline and respiratory impedance as an indicator of airway obstruction were studied in asthmatic patients. Each received multiple oral doses of a new sustained-release theophylline tablet formulation in amounts of 600 mg as the loading dose and maintenanace dose at a half of the loading dose. The theophylline concentrations in plasma and saliva were measured by substrate-labeled fluorescent immunoassay and respiratory impedance was measured by forced oscillatory technique. The data were analyzed by applying a one-compartment model using the computer program NONLIN. The apparent volume of distribution and plasma theophylline clearance were 0.336±0.054l/kg and 34.17±3.54ml/kg/hr, respectively. The mean apparent oral absorption rate constant was calculated to be 0.227±0.053 hr^<-1> and the apparent elimination rate constant was 0.101±0.015 hr^<-1> with an elimination half-life of 7.63±1.00 hr. The dose schedule in the present study indicated that steady state plasma concentrations in the range of 10-20μg/ml were maintained in four of the six patients. Furthermore, there was significant reduction in respiratory impedance at steady state trough times 84 and 96 hours compared with that obtained from pre-dose. These results showed that when steady state of plasma concentration exceeded 8μg/ml, respiratory impedance was reduced or unchanged. On the other hand, there was a good relationship between steady state trough concentrations in plasma and saliva (n=18, r=0.993, p<0.001). The mean saliva/plasma ratio of plasma theophylline concentration was 0.58±0.01 and the coefficient of variation for the variability was 9.0%. It is likely that once steady state trough plasma and saliva concentrations have been measured, monitoring of theophylline therapy using saliva measurements alone could be possible.
