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Please use this identifier to cite or link to this item: http://hdl.handle.net/11055/930
Title: A novel, palatable paediatric oral formulation of midazolam: pharmacokinetics, tolerability, efficacy and safety.
Authors: Salman S
Tang EKY
Cheung LC
Nguyen MN
Sommerfield D
Slevin L
Lim LY
von Ungern Sternberg BS
ANZCA/FPM Author: Sommerfield, D
von Ungern-Sternberg, BS
Keywords: Midazolam
Paediatrics
Drug Compounding
Taste
Citation: 73(12):1469-1477
Abstract: Midazolam is one of many bitter drugs where provision of a suitable oral paediatric formulation, particularly in the pre-anaesthetic setting, remains a challenge. To overcome this problem, a novel chocolate-based tablet formulation has been developed with positive pre-clinical results. To further investigate the potential of this formulation, 150 children aged 3-16 years who were prescribed midazolam as a premedication were randomly assigned to receive 0.5 mg.kg-1 either as the novel formulation or an intravenous solution given orally, which is the current standard at our institution. Tolerability was assessed by each child, parent and nurse using a 5-point facial hedonic scale and efficacy was determined as the time to onset of sedation. Blood samples for midazolam and 1-hydroxymidazolam levels were analysed using high-performance liquid chromatography. Population pharmacokinetics were evaluated using non-linear mixed effects modelling. The novel formulation had significantly improved tolerability scores from children, parents and nurses (all p < 0.001). Time to effect was not different between the groups (p = 0.140). The pharmacokinetics of midazolam and 1-hydroxymidazolam were able to be modelled simultaneously. The novel formulation was subject to a higher estimated first-pass metabolism compared with the intravenous solution (8.6% vs. 5.0%) and a significantly lower relative bioavailability of 82.1% (p = 0.013), with no other significant differences. Exposure relative to dose was in the range previously reported for midazolam syrup. We conclude that the novel chocolate-based formulation of midazolam provides improved tolerability while remaining efficacious with suitable pharmacokinetics when used as a premedicant for children.
URI: http://hdl.handle.net/11055/930
DOI: 10.1111/anae.14318
PubMed URL: https://www.ncbi.nlm.nih.gov/pubmed/29984832
Journal Title: Anaesthesia
Type: Journal Article
Affiliates: University of Western Australia
Curtin University
Princess Margaret Hospital for Children
Study/Trial: Randomized Controlled Clinical Trial/Controlled Clinical Trial
Appears in Collections:Scholarly and Clinical

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