THEOPHYLLINE POPULATION PHARMACOKINETICS FROM ROUTINE MONITORING DATAIN VERY PREMATURE-INFANTS WITH APNEA

1 Theophylline is commonly used in neonatology for the treatment and p rophylaxis of apnoea of prematurity, and during ventilator weaning. 2 NONMEM was used to study the population pharmacokinetics of intravenou s and oral theophylline from retrospective drug monitoring data in 82 premature neonates, weighing < 1500 g at birth, and less than or equal to 32 weeks gestational age. 3 Clearance (CL), volume of distribution (V), and oral bioavailability (F1) from liquid preparations were mode lled alone, and under the in-fluence of demographic and clinical covar iates, assuming a 1-compartment model with first-order elimination. 4 The final population models with influential co-variates were as follo ws: CL (1 h(-1))=0.0000123 body weight (g)+0.000377 *postnatal age (d ays); V(1)=0.000937 body weight (g); F=0.988. 5 The CL was lower and V was higher than previously reported for less premature neonates, ter m babies, and older children. 6 Predictive performance of the populati on models was evaluated by Bayesian forecasting in a similar, but inde pendent cohort of 30 infants. There was statistically insignificant bi as and imprecision between measured and predicted serum theophylline c oncentrations. 7 Based on the validated population models, recommended maintenance theophylline dosages are provided for infants aged betwee n 2 and 50 days, and weighing 700 to 2000 g.