The pharmacokinetics of theophylline in premature neonates during the first few days after birth.

The aims of the study were to estimate the pharmacokinetic parameters, clearance rate (CL), and volume of distribution (V) of theophylline in premature neonates during the first few days after birth, and to identify factors contributing to interindividual variability. The authors obtained 263 serum concentrations from 105 apneic premature neonates receiving intravenous (IV) theophylline. Mean (SD) birth weight and postnatal ages were 1.3 (0.3) kg and 1.1 (0.3) days, respectively. The data were analyzed using the nonlinear mixed effects model (NONMEM). A one-compartment model with first order elimination was used. The final models were: CL (L/h) = 0.006 * WGT 0.75 * P, V (L) = 0.63 * WGT, WGT = weight (kg) P = 1.47 with oxygen support and 1.0 without oxygen support. The CL in the study population was low, resulting in long half-lives. After inclusion of the above covariates, as well as interoccasion variability, the interindividual variability in CL was 56% and in V was 47%. Interoccasion variability in CL and V was 34% and 35% respectively. Theophylline pharmacokinetics are variable in the premature neonate during the first week of life, and this high variability makes it difficult to predict drug concentrations with the same degree of accuracy as in other populations.