Article date: April 2002
By: S. N. De Wildt, G. L. Kearns, W. C. J. Hop, D. J. Murry, S. M. Abdel‐Rahman, J. N. Van Den Anker, in Volume 53, Issue 4, pages 390-392
Aims To characterize the pharmacokinetics and metabolism of oral midazolam in 15 preterm infants.
Methods After an oral dose (0.1 mg kg−1), blood was drawn up to 24 h after administration. Midazolam and 1‐OH‐midazolam concentrations were determined with GC‐MS. In 8 out of these 15 patients the pharmacokinetics of intravenous midazolam was also studied.
Results Apparent oral clearance, apparent volume of distribution, plasma half‐life and 1‐OH‐Midazolam/Midazolam AUC ratio were [median (range)]: 2.7 [0.67–15.5] ml kg−1 min−1, 1.4 [0.3–12.1] l kg−1, 7.6 [1.2–15.1], h and 0.03 [0.01–0.96], respectively. Absolute bioavailability was 0.49 [0.12–1.0].
Conclusions Midazolam oral clearance is markedly decreased in preterm infants as compared with older children, probably because of immature CYP3A4 activity.
DOI: 10.1046/j.1365-2125.2002.01223.x
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