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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
Keywords: Midazolam
Drug Compounding
Source: 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 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.
DOI: 10.1111/anae.14318
PubMed URL:
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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