Theophylline pharmacokinetics in Thai children

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 micrograms/ml). Most patients had reproducible STC patterns during the study period; however, 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 (CI) = 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 18 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.(ABSTRACT TRUNCATED AT 250 WORDS)