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