Population pharmacokinetics of intravenous indomethacin in neonates with symptomatic patent ductus arteriosus

The population pharmacokinetics of intravenous indomethacin were investigated with 665 indomethacin serum concentrations from 83 neonates (mean ± SD: gestational age, 28.8 ± 2.5 weeks; postnatal age, 5.7 ± 4.7 days; birth weight, 1.13 ± 0.40 kg) receiving indomethacin for symptomatic patent ductus arteriosus. A one-compartment open model was used for pharmacokinetic analysis. Hypotheses were tested to determine which developmental and demographic data influenced clearance (CL) and volume of distribution (V_arca). In the final regression equation CL and V_arca were modeled as a function of body weight and postnatal age (PNA) from 0 to 20 days. Final estimates were as follows: CL (ml/hr) = 2.63·weight (kg) + 0.244·PNA (days) and V_arca (L) = 0.28·weight (kg) + 0.0041·PNA (days). The coefficients of variation for interindividual variability in CL and V_arca were 77% and 28%, respectively. Intraindividual variability was 19%. These mean population parameter estimates should prove useful in designing dosage regimens to achieve desired indomethacin concentrations for neonates from 0 to 20 days of age with symptomatic patent ductus arteriosus.