Does CYP3A4*1B change midazolam pharmacokinetics in preterm infants?

S. N. De Wildt, R. H.N. Van Schaik, D. J. Murry, N. M. Van Iperen, G. L. Kearns, J. N. Van Den Anker

Research output: Contribution to journalArticle

Abstract

The CYP3A4*1B mutation may be associated with altered CYP3A activity in adults. The CYP3A4 substrate midazolam (M) shows large interindividual PK differences in neonates. Thus, we studied the effect of CYP3A4*1B on M PK in preterm neonates. Methods: M (0.1 mg/kg) was administered as an oral bolus dose to 15 preterm infants (GA 26-34 wks, 3-13 days old, 11 Caucasians, 1 Mediterranean and 2 Caribbean Africans) followed by repeated blood sampling over 24 hrs. M and 1OHM concentrations were determined using GC-ELD; PK was determined with non compartmental analysis. CYP3A4*1B mutation analysis was carried out with PCR-RFLP. Results: M AUC0-∞ was significantly (p=0.043, Mann-Whitney test) lower in patients with the CYP3A4*1B genotype (1 A/G, 2 GG) compared to wildtype (12 A/A). M Cl/F (L/kg/h) was also increased, although not significantly (p=0.06) in the CYP3A4*1B carriers. Conclusions: The CYP3A4*1B appears to be associated with increased oral M clearance, which may reflect increased intestinal and/or hepatic CYP3A4 activity in preterm infants carrying the *1B allele.

Original languageEnglish (US)
Pages (from-to)P31
JournalClinical Pharmacology and Therapeutics
Volume69
Issue number2
StatePublished - 2001
Externally publishedYes

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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  • Cite this

    De Wildt, S. N., Van Schaik, R. H. N., Murry, D. J., Van Iperen, N. M., Kearns, G. L., & Van Den Anker, J. N. (2001). Does CYP3A4*1B change midazolam pharmacokinetics in preterm infants? Clinical Pharmacology and Therapeutics, 69(2), P31.