Indomethacin therapy in premature infants with patent ductus arteriosus - Determination of therapeutic plasma levels

T. F. Yeh, B. Achanti, H. Patel, R. S. Pildes

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

To determine the therapeutic range of plasma indomethacin levels for ductus closure, we evaluated the ductus response and renal side effects on two therapeutic regimens using different dosage; regimen I received 0.3 mg/kg q 24 h for a maximum of 3 doses, and regimen II received 0.1, 0.2 and 0.3 mg/kg at 24-hour intervals, for a maximum of 3 doses if needed. Infants in regimen I had significantly higher plasma indomethacin and higher ductus response rate than infants in regimen II. Urine output (U/O) was comparable between the regimens, but serum sodium was lower in regimen I than in regimen II. In both regimens, U/O and serum sodium returned to normal by 72 h. The plasma indomethacin levels at 12 h after 1 dose correlated significantly with ductus response and hyponatremia. There appeared to be a minimal level of plasma indomethacin above which U/O decreased; with a plasma level >170 ng/ml the majority (>97%) of infants showed a decrease in U/O. While there was a 50% or greater chance that ductus would close when the plasma levels reached 600 ng/ml or more, a great proportion of infants would also develop renal side effects. Thus, a safe therapeutic range of plasma indomethacin appeared to be very narrow. However, when the dose of indomethacin is increased to optimize constrictive response, there is no significant increase in incidence and severity of renal adverse effects. In view of the transient nature of renal side effects, they should not hinder indomethacin therapy if ductus closure is indicated.

Original languageEnglish
Pages (from-to)169-178
Number of pages10
JournalDevelopmental Pharmacology and Therapeutics
Volume12
Issue number4
Publication statusPublished - Jan 1 1989
Externally publishedYes

Fingerprint

Patent Ductus Arteriosus
Premature Infants
Indomethacin
Kidney
Urine
Therapeutics
Sodium
Hyponatremia
Serum
Incidence

ASJC Scopus subject areas

  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Pharmacology (medical)

Cite this

Indomethacin therapy in premature infants with patent ductus arteriosus - Determination of therapeutic plasma levels. / Yeh, T. F.; Achanti, B.; Patel, H.; Pildes, R. S.

In: Developmental Pharmacology and Therapeutics, Vol. 12, No. 4, 01.01.1989, p. 169-178.

Research output: Contribution to journalArticle

@article{e9b9b33c05604f33b036fd8b09c2a7ce,
title = "Indomethacin therapy in premature infants with patent ductus arteriosus - Determination of therapeutic plasma levels",
abstract = "To determine the therapeutic range of plasma indomethacin levels for ductus closure, we evaluated the ductus response and renal side effects on two therapeutic regimens using different dosage; regimen I received 0.3 mg/kg q 24 h for a maximum of 3 doses, and regimen II received 0.1, 0.2 and 0.3 mg/kg at 24-hour intervals, for a maximum of 3 doses if needed. Infants in regimen I had significantly higher plasma indomethacin and higher ductus response rate than infants in regimen II. Urine output (U/O) was comparable between the regimens, but serum sodium was lower in regimen I than in regimen II. In both regimens, U/O and serum sodium returned to normal by 72 h. The plasma indomethacin levels at 12 h after 1 dose correlated significantly with ductus response and hyponatremia. There appeared to be a minimal level of plasma indomethacin above which U/O decreased; with a plasma level >170 ng/ml the majority (>97{\%}) of infants showed a decrease in U/O. While there was a 50{\%} or greater chance that ductus would close when the plasma levels reached 600 ng/ml or more, a great proportion of infants would also develop renal side effects. Thus, a safe therapeutic range of plasma indomethacin appeared to be very narrow. However, when the dose of indomethacin is increased to optimize constrictive response, there is no significant increase in incidence and severity of renal adverse effects. In view of the transient nature of renal side effects, they should not hinder indomethacin therapy if ductus closure is indicated.",
author = "Yeh, {T. F.} and B. Achanti and H. Patel and Pildes, {R. S.}",
year = "1989",
month = "1",
day = "1",
language = "English",
volume = "12",
pages = "169--178",
journal = "Developmental Pharmacology and Therapeutics",
issn = "0379-8305",
publisher = "S. Karger AG",
number = "4",

}

TY - JOUR

T1 - Indomethacin therapy in premature infants with patent ductus arteriosus - Determination of therapeutic plasma levels

AU - Yeh, T. F.

AU - Achanti, B.

AU - Patel, H.

AU - Pildes, R. S.

PY - 1989/1/1

Y1 - 1989/1/1

N2 - To determine the therapeutic range of plasma indomethacin levels for ductus closure, we evaluated the ductus response and renal side effects on two therapeutic regimens using different dosage; regimen I received 0.3 mg/kg q 24 h for a maximum of 3 doses, and regimen II received 0.1, 0.2 and 0.3 mg/kg at 24-hour intervals, for a maximum of 3 doses if needed. Infants in regimen I had significantly higher plasma indomethacin and higher ductus response rate than infants in regimen II. Urine output (U/O) was comparable between the regimens, but serum sodium was lower in regimen I than in regimen II. In both regimens, U/O and serum sodium returned to normal by 72 h. The plasma indomethacin levels at 12 h after 1 dose correlated significantly with ductus response and hyponatremia. There appeared to be a minimal level of plasma indomethacin above which U/O decreased; with a plasma level >170 ng/ml the majority (>97%) of infants showed a decrease in U/O. While there was a 50% or greater chance that ductus would close when the plasma levels reached 600 ng/ml or more, a great proportion of infants would also develop renal side effects. Thus, a safe therapeutic range of plasma indomethacin appeared to be very narrow. However, when the dose of indomethacin is increased to optimize constrictive response, there is no significant increase in incidence and severity of renal adverse effects. In view of the transient nature of renal side effects, they should not hinder indomethacin therapy if ductus closure is indicated.

AB - To determine the therapeutic range of plasma indomethacin levels for ductus closure, we evaluated the ductus response and renal side effects on two therapeutic regimens using different dosage; regimen I received 0.3 mg/kg q 24 h for a maximum of 3 doses, and regimen II received 0.1, 0.2 and 0.3 mg/kg at 24-hour intervals, for a maximum of 3 doses if needed. Infants in regimen I had significantly higher plasma indomethacin and higher ductus response rate than infants in regimen II. Urine output (U/O) was comparable between the regimens, but serum sodium was lower in regimen I than in regimen II. In both regimens, U/O and serum sodium returned to normal by 72 h. The plasma indomethacin levels at 12 h after 1 dose correlated significantly with ductus response and hyponatremia. There appeared to be a minimal level of plasma indomethacin above which U/O decreased; with a plasma level >170 ng/ml the majority (>97%) of infants showed a decrease in U/O. While there was a 50% or greater chance that ductus would close when the plasma levels reached 600 ng/ml or more, a great proportion of infants would also develop renal side effects. Thus, a safe therapeutic range of plasma indomethacin appeared to be very narrow. However, when the dose of indomethacin is increased to optimize constrictive response, there is no significant increase in incidence and severity of renal adverse effects. In view of the transient nature of renal side effects, they should not hinder indomethacin therapy if ductus closure is indicated.

UR - http://www.scopus.com/inward/record.url?scp=0024390247&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0024390247&partnerID=8YFLogxK

M3 - Article

C2 - 2766920

AN - SCOPUS:0024390247

VL - 12

SP - 169

EP - 178

JO - Developmental Pharmacology and Therapeutics

JF - Developmental Pharmacology and Therapeutics

SN - 0379-8305

IS - 4

ER -