Pharmacokinetics and metabolism of oral midazolam in preterm infants

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Abstract

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.

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