Pharmacokinetics and metabolism of oral midazolam in preterm infants

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.