Theophylline pharmacokinetics in Thai children

Abstract

To validate a previously suggested dosing regimen of aminophylline administration for Thai children, we enrolled 13 asthmatic Thai children (5 girls and 8 boys) between the ages of 7.5-13.4 years (mean = 10.4 years) into a 36-hour, multiple-dose, oral theophylline pharmacokinetic study using plain aminophylline tablets at a dosage of 5 mg of theophylline base/kg every 8 hours. All patients were studied in the steady state. Blood samples were obtained every 2 hours for 24 hours; thereafter, samples were obtained more frequently for another 12 hours to determine theophylline pharmacokinetic parameters. Serum theophylline concentrations (STC) were assayed with a fluorescence polarization immunoassay method (TDX). Significant interpatient variations in STCs were observed. Five patients had peak STCs in the toxic range ( > 20 μg/ml). Most patients had reproducible STC patterns during the study period; how ever, marked variations of STCs were observed with a mean percent of fluctuations {(Cmax-Cmin)/Cmin *100} of 535.6%. Using the PC Nonlin computer interpolation program by a modification with a baseline decay method and the Lagrange polynominal interpolation technique, approximate pharmacokinetic parameters were calculated and the results were as follows: plasma half life (t1/2) = 3.08 hours, elimination rate constant (Kel) = 0.26 hour-1, absorption rate constant (Ka) = 2.21 hour-1, volume of distribution (Vd) = 0.23 l/kg and plasma clearance (Cl) = 56 ml/kg/hour. Since these calculated parameters could be imprecise due to delayed absorption of oral theophylline dosages, a single-dose intravenous theophylline pharmacokinetic study was further examined in another 13 patients (age range = 7-12 years, mean = 8.9 years) to determine more accurate pharmacokinetic data using intravenous aminophylline at dosage of 5.8 mg/kg. Data derived from this part of the study were t 1/2 = 4.25 hours, Kel = 0.19 hour-1, Vd = 0.44 l/kg, Clp = 90 ml/kg/hour and a mean residence time (MRT) of 5.84 hours. From these data, we conclude that theophylline pharmacokinetic data in this group of Thai children did not differ significantly form Caucasian children in the same age range. We therefore suggest that the routine dose regimen as recommended for Caucasian children in this age group may be applicable to Thai children as well.