Indomethacin exposure increases midazolam clearance in preterm infants

J. N. Van Den Anker, S. N. De Wildt, D. J. Murry, W. C.J. Hop, S. Abdel-Rahman, G. L. Kearns

Research output: Contribution to journalArticle

Abstract

We determined the effect of clinical parameters and indomethacin on PK of IV medazolam (M) and 1-OH-midazolam (1OHM) in neonates. Methods: M (0.1 mg/kg) was administered to 24 preterm infants (GA 26-34 wks, 3-13 days old) as a 30 minute infusion. Blood samples were taken at 0,0.5, 1,2,4,6,12 and 24 hours after M administration. M and 1OHM concentrations were determined using GCECD; LLD Ing/ml (M) and 0.2 ng/ml (1OHM). PK parameters were estimated using non-compartmental methods. Associations between clinical parameters/co-medication and M PK were analyzed with Spearman's correlation and multivariate analysis. Results: Both postnatal age and indomethacin administration (for PDA) showed a significant relationship with M Cl (L/h/kg). Multiple regression showed that M Cl was increased after indomethacin treatment (p=0.01), while, adjusted for this effect, there was no predictive value for postnatal age (p=0.77). Discussion: The indomethacin-related increase of M Cl shows that renal and/or hemodynamic factors may be important determinants M PK in preterm infants in addition to hepatic metabolism.

Original languageEnglish (US)
Pages (from-to)P82
JournalClinical Pharmacology and Therapeutics
Volume69
Issue number2
StatePublished - Jan 1 2001

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Midazolam
Premature Infants
Indomethacin
Multivariate Analysis
Hemodynamics
Newborn Infant
Kidney
Liver
hydroxide ion
Therapeutics

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

Cite this

Van Den Anker, J. N., De Wildt, S. N., Murry, D. J., Hop, W. C. J., Abdel-Rahman, S., & Kearns, G. L. (2001). Indomethacin exposure increases midazolam clearance in preterm infants. Clinical Pharmacology and Therapeutics, 69(2), P82.

Indomethacin exposure increases midazolam clearance in preterm infants. / Van Den Anker, J. N.; De Wildt, S. N.; Murry, D. J.; Hop, W. C.J.; Abdel-Rahman, S.; Kearns, G. L.

In: Clinical Pharmacology and Therapeutics, Vol. 69, No. 2, 01.01.2001, p. P82.

Research output: Contribution to journalArticle

Van Den Anker, JN, De Wildt, SN, Murry, DJ, Hop, WCJ, Abdel-Rahman, S & Kearns, GL 2001, 'Indomethacin exposure increases midazolam clearance in preterm infants', Clinical Pharmacology and Therapeutics, vol. 69, no. 2, pp. P82.
Van Den Anker JN, De Wildt SN, Murry DJ, Hop WCJ, Abdel-Rahman S, Kearns GL. Indomethacin exposure increases midazolam clearance in preterm infants. Clinical Pharmacology and Therapeutics. 2001 Jan 1;69(2):P82.
Van Den Anker, J. N. ; De Wildt, S. N. ; Murry, D. J. ; Hop, W. C.J. ; Abdel-Rahman, S. ; Kearns, G. L. / Indomethacin exposure increases midazolam clearance in preterm infants. In: Clinical Pharmacology and Therapeutics. 2001 ; Vol. 69, No. 2. pp. P82.
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