Pharmacokinetics and metabolism of oral midazolam in preterm infants
- 28 April 2002
- journal article
- research article
- Published by Wiley in British Journal of Clinical Pharmacology
- Vol. 53 (4), 390-392
- https://doi.org/10.1046/j.1365-2125.2002.01223.x
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.Keywords
This publication has 13 references indexed in Scilit:
- Enterocytic CYP3A4 in a paediatric population: developmental changes and the effect of coeliac disease and cystic fibrosisBritish Journal of Clinical Pharmacology, 2001
- Population Pharmacokinetic Modeling in Very Premature Infants Receiving Midazolam during Mechanical VentilationAnesthesiology, 1999
- Cytochrome P450 3AClinical Pharmacokinetics, 1999
- Clinical Pharmacokinetics of Sedatives in NeonatesClinical Pharmacokinetics, 1996
- Oral first-pass elimination of midazolam involves both gastrointestinal and hepatic CYP3A-mediated metabolism*Clinical Pharmacology & Therapeutics, 1996
- First-pass metabolism of midazolam by the human intestine*Clinical Pharmacology & Therapeutics, 1995
- Population pharmacokinetics of midazolam in neonatesClinical Pharmacology & Therapeutics, 1994
- Regioselective biotransformation of midazolam by members of the human cytochrome P450 3A (CYP3A) subfamilyBiochemical Pharmacology, 1994
- Pharmacokinetic-pharmacodynamic modeling of the central nervous system effects of midazolam and its main metabolite α-hydroxymidazolam in healthy volunteersClinical Pharmacology & Therapeutics, 1992
- The pharmacokinetics of midazolam in manEuropean Journal of Clinical Pharmacology, 1981