Disposition of Intravenous Theophylline in Asthmatic Children: Bayesian Approach vs Direct Pharmacokinetic Calculations
Ehab El Desoky (1), Mohamed H. Ghazal (2), Moussa A. Mohamed (1) and Ulrich Klotz (1,#)
(1) Pharmacology and (2) Pediatric Departments, Faculty of Medicine,
Assuit University, 71516 Assuit, Egypt
(#) Present address: Dr. Margarete Fischer Bosch Institute of Clinical Pharmacology, 70376 Stuttgart, Germany
Abstract: 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 samples 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 (t1/2) 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 compared to the parameters calculated by a standard pharmacokinetic procedure (SC). Therapeutic steady state plasma levels around 12 microg/ml were rapidly achieved, and the pharmacokinetic parameters (CL = 1.1 - 1.5 ml/min/kg, Vd = 0.44 - 0.50 l/kg, t1/2 = 3.5 - 5.4 hr) differed slightly between the 3 methods applied. There was a significant linear correlation between the Bayesian-derived and SC-derived pharmacokinetic parameters. However the method Bay 1 seems to overestimate the elimination rate of theophylline more than Bay 3 does. In conclusion, Bayesian-based therapeutic plasma level monitoring (Bay 3 are better than Bay 1) can be utilized for individualized pharmacokinetic calculations and proper dosage predictions of theophylline in pediatric patients.
Keywords: Theophylline, Pediatrics, Pharmacokinetics, Bayesian