Document Detail

Intravenous indometacin in preterm infants with symptomatic patent ductus arteriosus. A population pharmacokinetic study.
MedLine Citation:
PMID:  15327584     Owner:  NLM     Status:  MEDLINE    
AIMS: To characterize the population pharmacokinetics of indometacin in preterm infants with symptomatic patent ductus arteriosus and to investigate the influence of various factors on the response to treatment.
METHODS: Data were collected from 35 infants (gestational age 25-34 weeks; postnatal age 1-77 days) in neonatal units in Belfast and Copenhagen. Infants received an initial course of up to three doses of intravenous indometacin (0.1-0.2 mg kg(-1)) as considered appropriate by the treating physician. For those infants who did not respond to therapy or in whom the ductus reopened, a second course was sometimes given. Population analysis of the 185 plasma concentrations obtained was conducted using NONMEM and pharmacokinetic and demographic differences between responders and nonresponders were compared.
RESULTS: The concentration-time course of indometacin was best described by a one-compartment model. The final population parameter estimates of clearance (CL) and volume of distribution (V) (standardized to the median weight of 1.17 kg) were 0.00711 l h(-1) and 0.266 l, respectively. CL increased from birth by approximately 3.38% per day and V by approximately 1.47% per day. Concomitant digoxin therapy resulted in a 30% decrease in V. Interindividual variability in CL and V was 41% and 21%, respectively. Interoccasion variability for CL was 43%. Residual variability corresponded to a standard deviation of 0.148 mg l(-1). Closure occurred in 75% of infants with a plasma concentration > or = 0.4 mg l(-1) 24 h after the last dose.
CONCLUSIONS: Dosing regimens for indometacin should take into account the weight and postnatal age of the infant and any concomitant digoxin therapy. The population estimates can be used to determine typical values of CL and V allowing the prediction of individualized doses of indometacin that should increase the probability of achieving a 24 h plasma concentration > or = 0.4 mg l(-1). Although the pharmacokinetic estimates will be affected by both interindividual and within-individual variation, it is anticipated that this approach will decrease the variability of exposure and optimize treatment outcome.
J M Smyth; P S Collier; M Darwish; J S Millership; H L Halliday; S Petersen; J C McElnay
Related Documents :
2766924 - Does indomethacin affect the control of breathing in premature infants?
17024144 - New insights into spontaneous intestinal perforation using a national data set (3): ant...
3050004 - Oligohydramnios, renal insufficiency, and ileal perforation in preterm infants after in...
10752764 - The stressed neonatal kidney: from pathophysiology to clinical management of neonatal v...
7824584 - The breathing bear: effects on respiration in premature infants.
25239374 - Interaction between cadmium (cd), selenium (se) and oxidative stress biomarkers in heal...
Publication Detail:
Type:  Journal Article; Multicenter Study; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  British journal of clinical pharmacology     Volume:  58     ISSN:  0306-5251     ISO Abbreviation:  Br J Clin Pharmacol     Publication Date:  2004 Sep 
Date Detail:
Created Date:  2004-08-25     Completed Date:  2004-12-17     Revised Date:  2013-06-09    
Medline Journal Info:
Nlm Unique ID:  7503323     Medline TA:  Br J Clin Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  249-58     Citation Subset:  IM    
Clinical and Practice Research Group, School of Pharmacy, Queen's University, Belfast, UK.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Cardiovascular Agents / administration & dosage*,  pharmacokinetics
Ductus Arteriosus, Patent / drug therapy*
Indomethacin / administration & dosage*,  pharmacokinetics
Infant, Newborn
Infant, Premature
Infusions, Intravenous
Reg. No./Substance:
0/Cardiovascular Agents; 53-86-1/Indomethacin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Alpha-lipoic acid does not acutely affect resistance and conduit artery function or oxidative stress...
Next Document:  Vancomycin pharmacokinetics in critically ill patients receiving continuous venovenous haemodiafiltr...