Abstract

The effect of surfactant administration for respiratory distress syndrome (RDS) on indomethacin (INDO) pharmacodynamics and dosing requirements for patent ductus arteriosus (PDA) closure and renal toxicity was evaluated. A 22-year prospective cohort study including 442 INDO-treated patients given 466 INDO treatment courses. The database included demographic information, medical problems, and medications. Neonates with a PDA confirmed by echocardiography were treated with INDO, 0.25-0.3 mg/kg. Subsequent INDO dosing was based on a combined pharmacokinetic/pharmacodynamic (PK/PD) approach. Data were fit to an Emax model and ANOVA was used to compare mean closure levels between groups. PDA closure was successful in 405 of 442 patients (91.6%) and in 434 of 466 treatment courses (93.1%) using an individualized PK/PD dosing approach. Renal toxicity was documented in 56 of 442 patients (12.7%) or 56 of 466 treatment courses (12.0%). Patients not treated with synthetic surfactant trended toward lower mean INDO concentrations at PDA closure compared to patients treated with synthetic surfactant (1.65 vs. 2.01 mg/l; P > 0.05) and significantly lower mean INDO concentrations at PDA closure compared to patients treated with natural surfactant (1.65 vs. 2.15 mg/l; P < 0.002). This requires an increased total dose of ~0.3 mg/kg or an individual dose increase of 0.1 mg/kg. Administration of natural or synthetic surfactant for RDS may increase the INDO concentrations and doses needed for PDA closure in premature infants.

Links

Publisher Full Text

Authors

McPherson C, Gal P, Ransom JL, Carlos RQ, Dimaguila MA, Smith M, Davonzo C, Wimmer JE

Institution

Pharmacy and Newborn Medicine, St Louis Children's Hospital, St Louis, MO, USA.

Source

Pediatric cardiology 31:4 2010 May pg 505-10

MeSH

Animals
Anti-Inflammatory Agents, Non-Steroidal
Biological Availability
Biological Products
Cohort Studies
Dose-Response Relationship, Drug
Drug Administration Schedule
Drug Combinations
Drug Interactions
Ductus Arteriosus, Patent
Echocardiography
Echocardiography, Doppler, Color
Fatty Alcohols
Guideline Adherence
Humans
Indomethacin
Infant, Newborn
Intensive Care Units, Neonatal
Kidney
Metabolic Clearance Rate
Phosphorylcholine
Polyethylene Glycols
Prospective Studies
Pulmonary Surfactants
Respiratory Distress Syndrome, Newborn

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

20063159