Exploring the pharmacokinetics of oral ketamine in children undergoing burns procedures

Brunette, Katharine E. J., Anderson, Brian J., Thomas, Jennifer, Wiesner, Lubbe, Herd, David W. and Schulein, Simone (2011) Exploring the pharmacokinetics of oral ketamine in children undergoing burns procedures. Paediatric Anaesthesia, 21 6: 653-662. doi:10.1111/j.1460-9592.2011.03548.x

Author Brunette, Katharine E. J.
Anderson, Brian J.
Thomas, Jennifer
Wiesner, Lubbe
Herd, David W.
Schulein, Simone
Title Exploring the pharmacokinetics of oral ketamine in children undergoing burns procedures
Journal name Paediatric Anaesthesia   Check publisher's open access policy
ISSN 1155-5645
Publication date 2011-06
Year available 2011
Sub-type Article (original research)
DOI 10.1111/j.1460-9592.2011.03548.x
Open Access Status Not yet assessed
Volume 21
Issue 6
Start page 653
End page 662
Total pages 10
Place of publication Chichester, West Sussex, United Kingdom
Publisher Wiley-Blackwell Publishing
Language eng
Formatted abstract
Aims: The aim of this study was to describe ketamine pharmacokinetics when administered orally to children suffering from burn injury in >10% body surface area.

Methods: Children (n = 20) were given ketamine 5 or 10 mg·kg-1 orally 20 min prior to presentation for surgical procedures. Anesthesia during procedures was maintained with a volatile anesthetic agent. Additional intravenous ketamine was given as a bolus (0.5-1 mg·kg-1) to nine children during the procedure while a further nine children were given an infusion (0.1 mg·kg-1·h-1) continued for 4-19 h after the procedure. Blood was assayed for ketamine and norketamine on six occasions over the study duration of 8-24 h. Data were pooled with those from an earlier analysis (621 observations from 70 subjects). An additional time-concentration profile from an adult given oral ketamine was gleaned from the literature (17 observations). A population analysis was undertaken using nonlinear mixed-effects models.

The pooled analysis comprised 852 observations from 91 subjects. There were 20 children who presented for procedures related to burns management (age 3.5 sd 2.1 years, range 1-8 years; weight 14.7 sd 4.9 kg, range 7.9-25 kg), and these children contributed 214 ketamine and norketamine observations. A two-compartment (central, peripheral) linear disposition model fitted data better than a one-compartment model. Bioavailability of the oral formulation was 0.45 (90% CI 0.33, 0.58). Absorption half-time was 59 (90% CI 29.4, 109.2) min and had high between-subject variability (BSV 148%). Population parameter estimates, standardized to a 70-kg person, were central volume 21.1 (BSV 47.1%) l·70 kg-1, peripheral volume of distribution 109 (27.5%) l·70 kg-1, clearance 81.3 (46.1%) l·h-1·70 kg-1, and inter-compartment clearance 259 (50.1%) l·h-1·70 kg-1. Under the assumption that all ketamine was converted to norketamine, the volume of the metabolite was 151.9 (BSV 39.1%) l·70 kg-1 with an elimination clearance of 64.4 (BSV 63.4%) l·h-1·70 kg-1 and a rate constant for intermediate compartments of 26.2 (BSV 52.1%) h-1·70 kg-1.

Conclusions: The ketamine pharmacokinetics in children with minor burns are similar to those without burns. The peak ratio of norketamine/ketamine at 1 h is 2.8 after oral administration allowing an analgesic contribution from the metabolite at this time. There is low relative bioavailability (<0.5) and slow variable absorption. Dose simulation in a child (3.5 years, 15 kg) suggests a dose regimen of oral ketamine 10 mg·kg-1 followed by intravenous ketamine 1 mg·kg-1 i.v. with the advent of short-duration surgical dressing change at 45 min.
Keyword Burns
Oral dosing
Procedural sedation
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
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Citation counts: TR Web of Science Citation Count  Cited 8 times in Thomson Reuters Web of Science Article | Citations
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