Theophylline Phannacokinetics in Thai Children

To validate a previously suggested dosing regimen of aminophylline administration for Thai children 1, we enrolled 13 asthmatic Thai children (5 girts and 8 boys) between the ages of 7.5-13.4 years (mean=10.4 years) Into a 36-hour, multiple-dose, oral theophylline pharmacoklnetlc study using plain aminophylline tablets at a dosage of 5 rna of theophylline ba_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 obtalnad more frequently for another 12 hours to determine theophylline pharmacoklnetlc parameters. Serum theophylline concentrstlons (STO) were assayad with a fluorescence polarization Immunoassay method (TOX). SignifIcant Interpatlant variations In STCs were observed. Five patlants had peak STCs In the toxic range (>20 ",glml). Most patients had reproducible STC patterns during the study period; however, markad variations of STCs were observad with a mean percent of fluctuations {(Cmax-Cmln)/Cmln *100} of 535.6%. Using the PC Nonlin computer Interpolation program by a modification with a baseline decay method and the Lagrange polynomlnal interpolation technique, approximate pharo macoklnetlc 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 (Ke) =2.21 hour-1, volume of distribution (Vel) = 0.23 IIkg and plasma clearance (CI) =56 mlfkglhour. Since these calculated parameters could be Imprecise due to delayed absorption of oral theophylline dosages, a slngle-dose Intr. venous theophylline pharmacoklnetlc study was further examlnad In another 13 patients (age range =7-12 years, mean =8.9 years) to determine more accurate pharmacoklnetlc data using Intravenous amlnqJhylllne at dosage of 5.8 mg/kg. Data derived from this part ofthe study were t 112 = 4.25 hours, Kel =0.19 hour-1, Vd = 0.44 /lkg, Clp =90 mllkglhour and a mean residence time (MRT) of 5.84 hours. From these data, we conclude that theophylline ~armacoklnetlc data In this group of Thai children did not differ significantly form Caucasian children In the sam e age range. We therefore suggest that the routine dose regimen as recommended for Caucsslanchlldren In this age group may be applicable to Thai children as well.