THEOPHYLLINE PHARMACOKINETICS IN THAI CHILDREN

To validate a previously suggested dosing regimen of aminophylline adm inistration for Thai children(1), we enrolled 13 asthmatic Thai childr en (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 pharmacokine tic study using plain aminophylline tablets at a dosage of 5 mg of the ophylline base/kg every 8 hours. All patients were studied in the stea dy state. Blood samples were obtained every 2 hours for 24 hours; ther eafter, samples were obtained more frequently for another 12 hours to determine theophylline pharmacokinetic parameters. Serum theophylline concentrations (STC) were assayed with a fluorescence polarization imm unoassay method (TDX). Significant interpatient variations in STCs wer e observed. Five patients had peak STCs in the toxic range (>20 mu g/m l). Most patients had reproducible STC patterns during the study perio d; however, marked variations of STCs were observed with a mean percen t of fluctuations {(Cmax-Cmin)/Cmin 100} of 535.6%. Using the PC Nonl in computer interpolation program by a modification with a baseline de cay method and the Lagrange polynominal interpolation technique, appro ximate pharmacokinetic parameters were calculated and the results were as follows: plasma half life (t1/2) = 3.08 hours, elimination rate co nstant (Kel) = 0.26 hour(-1), absorption rate constant (Ka) = 2.21 hou r(-1), volume of distribution (Vd) = 0.23 l/kg and plasma clearance (C I) = 56 ml/kg/hour. Since these calculated parameters could be impreci se due to delayed absorption of oral theophylline dosages, a single-do se 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 aminoph ylline at dosage of 5.8 mg/kg. Data derived from this part of the stud y were t1/2 = 4.25 hours, Kel = 0.19 hour(-1), Vd = 0.44 l/kg, Clp = 9 0 ml/kg/hour and a mean residence time (MRT) of 5.84 hours. From these data, we conclude that theophylline pharmacokinetic data in this grou p of Thai children did not differ significantly form Caucasian childre n in the same age range. We therefore suggest that the routine dose re gimen as recommended for Caucasian children in this age group may be a pplicable to Thai children as well.