Influence of chronic dosing on theophylline clearance.

Abstract

Theophylline clearance was studied in normal healthy volunteers before and after chronic oral dosing. Oral theophylline clearance showed a significant decrease (P less than 0.001) from 59.3 +/‐ 6.48 ml/min (mean +/‐ s.e. mean, n = 10) to 48.0 +/‐ 6.4 ml/min. Steady‐state intravenous clearance decreased by 26 +/‐ 2% from 55.1 +/‐ 7.7 ml/min to 41.0 +/‐ 5.96 ml/min (mean +/‐ s.e. mean, n = 6; P less than 0.001) at constant steady‐state intravenous test concentrations (mean 15.0 +/‐ 1.6 micrograms/ml after chronic oral dosing), excluding significant concentration dependence. Extrapolation of acute clearance findings to maintenance requirement may not be valid even in the same individual, with theophylline therapy requiring on‐going review beyond acute stabilisation.

Theophylline Pooled Michaelis-Menten Parameters (Vmax and Km) and Implications

“…The author agrees with the conclusions of Efthimiou et al (1984) that 'extrap~ olation of acute clearance findings to maintenance requirement may not be valid even in the same individual, with theophylline therapy requiring ongoing review beyond acute stabilisation'.…”

Influence of chronic dosing on theophylline clearance.

“…Thus, concentration-dependent changes of theophylline clearance cannot be excluded as a possible cause for the differences in oral clearance that were observed between the single dose and chronic dose studies. Influence of chronic dosing on theophylline clearance Vozeh & Follath (1985) have given two reasons in criticizing our exclusion of concentration dependence as a possible mechanism for the difference in oral clearances of theophylline (Efthimiou et al, 1984). The first criticism, regarding the short sampling time compared with the terminal half-life, is valid when applied to the oral clearance determined from the first single oral dose.…”

“…Thus, Voieh & Follath (1985) argue that basing the intravenous loading dose on the oral clearance value will bias the apparent intravenous clearance value obtained towards the oral clearance value. The premise of this argument is false because, as stated in our paper (Efthimiou et al, 1984), the intravenous loading dose was calculated for each subject using a volume of distribution of 0.5 l/kg, which is a literature value. The oral clearance value was used only in the calculation of the maintenance infusion rate and not the loading dose.…”

“…Before accepting the statement of Efthimiou et al (1984) in their paper on 'Influence of chronic dosing on theophylline clearance' saying that the therapeutic implications of their results are basic, some points must be raised concerning pharmacokinetics.…”

Influence of chronic dosing on theophylline clearance.

“…Influence of chronic dosing on theophylline clearance Vozeh & Follath (1985) have given two reasons in criticizing our exclusion of concentration dependence as a possible mechanism for the difference in oral clearances of theophylline (Efthimiou et al, 1984).…”