DISPOSITION OF INTRAVENOUS THEOPHYLLINE IN ASTHMATIC-CHILDREN - BAYESIAN-APPROACH VS DIRECT PHARMACOKINETIC CALCULATIONS

Fifteen children (mean age+/-SD: 6.4+/-3.4, range: 2-12 years) with an acute asthma attack were treated by an intravenous dosage regimen of theophylline (30 min loading infusion of 6 mg/kg body weight followed by a constant infusion of 1 mg/kg, twice for 6 hr each). Three blood s amples were drawn (each 15 min after the bolus infusion and after the two infusion periods of 6 hr). Plasma clearance (CL), apparent volume of distribution (Vd) and elimination half-life (t(1/2)) were estimated by the Bayesian approach using either only the first peak level (Bay 1) or all three monitored concentrations (Bay 3). These values were co mpared to the parameters calculated by a standard pharmacokinetic proc edure (SC). Therapeutic steady state plasma levels around 12 mu g/ml w ere rapidly achieved, and the pharmacokinetic parameters (CL=1.1-1.5 m l/min/kg, Vd=0.44-0.50 l/kg, t(1/2)=3.5-5.4 hr) differed slightly betw een the 3 methods applied. There was a significant linear correlation between the Bayesian-derived and SC-derived pharmacokinetic parameters . However the method Bay I seems to overestimate the elimination rate of theophylline more than Bay 3 does. In conclusion, Bayesian-based th erapeutic plasma level monitoring (Bay 3 are better than Bay 1) can be utilized for individualized pharmacokinetic calculations and proper d osage predictions of theophylline in pediatric patients.