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Population pharmacokinetics of intravenous indomethacin in neonates with symptomatic patent ductus arteriosus
Author(s) -
Wiest Donald B,
Pinson Julianne B,
Gal Peter S,
Brundage Richard C,
Schall S,
Ransom J Laurence,
Weaver Richard L,
Purohit Dilip,
Brown Y
Publication year - 1991
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1991.65
Subject(s) - ductus arteriosus , pharmacokinetics , medicine , gestational age , volume of distribution , population , birth weight , body weight , anesthesia , clinical pharmacology , pediatrics , pharmacology , pregnancy , biology , genetics , environmental health
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 area ). In the final regression equation CL and V area 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 area (L) = 0.28 · weight (kg) + 0.0041 · PNA (days). The coefficients of variation for interindividual variability in CL and V area 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. Clinical Pharmacology and Therapeutics (1991) 49, 550–557; doi: 10.1038/clpt.1991.65