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(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.
Wiest
D B
DB
Department of Clinical Pharmacy, Medical University of South Carolina, Charleston 29425.
Pinson
J B
JB
Gal
P S
PS
Brundage
R C
RC
Schall
S
S
Ransom
J L
JL
Weaver
R L
RL
Purohit
D
D
Brown
Y
Y
D001724:Birth Weight; D004341:Drug Evaluation; D004374:Ductus Arteriosus, Patent / Q000188:drug therapy / Q000378:metabolism*; D005260:Female; D005865:Gestational Age; D006801:Humans; D007213:Indomethacin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D007231:Infant, Newborn; D007275:Injections, Intravenous; D016014:Linear Models; D008297:Male
D007213:Indomethacin