dc.contributor.author |
Dawes, JM |
en |
dc.contributor.author |
Cooke, EM |
en |
dc.contributor.author |
Sturge, Jacqueline |
en |
dc.contributor.author |
Brand, KA |
en |
dc.contributor.author |
Winton, P |
en |
dc.contributor.author |
Jimenez-Mendez, R |
en |
dc.contributor.author |
Aleksa, K |
en |
dc.contributor.author |
Lauder, GR |
en |
dc.contributor.author |
Carleton, BC |
en |
dc.contributor.author |
Koren, G |
en |
dc.contributor.author |
Rieder, MJ |
en |
dc.contributor.author |
Anderson, Brian |
en |
dc.contributor.author |
Montgomery, CJ |
en |
dc.contributor.editor |
Bosenberg, A |
en |
dc.date.accessioned |
2017-03-09T03:42:54Z |
en |
dc.date.issued |
2017-01 |
en |
dc.identifier.citation |
Pediatric Anesthesia 27(1):28-36 Jan 2017 |
en |
dc.identifier.issn |
1155-5645 |
en |
dc.identifier.uri |
http://hdl.handle.net/2292/32115 |
en |
dc.description.abstract |
BACKGROUND: Oral morphine has been proposed as an effective and safe alternative to codeine for after-discharge pain in children following surgery but there are few data guiding an optimum safe oral dose. AIMS: The aim of this study was to characterize the absorption pharmacokinetics of enteral morphine in order to simulate time-concentration profiles in children given common oral morphine dose regimens. METHODS: Children (2-6 years, n = 34) undergoing elective surgery and requiring opioid analgesia were randomized to receive preoperative oral morphine (100 mcg·kg(-1) , 200 mcg·kg(-1) , 300 mcg·kg(-1) ). Blood sampling for morphine assay was performed at 30, 60, 90, 120, 180, and 240 min. Morphine serum concentrations were determined by liquid chromatography-mass spectroscopy and pharmacokinetic parameters were calculated using nonlinear mixed effects models. Current data were pooled with published time-concentration profiles from children (n = 1059, age 23 weeks postmenstrual age - 3 years) administered intravenous morphine, to determine oral bioavailability (F), absorption lag time (TLAG ), and absorption half-time (TABS ). These parameter estimates were used to predict concentrations in children given oral morphine (100, 200, 300, 400, 500 mcg·kg(-1) ) at different dosing intervals (3, 4, 5, 6, 8, 12 h). RESULTS: The oral morphine formulation had F 0.298 (CV 36.5%), TLAG 0.45 (CV 63.6%) h and TABS 0.71 (CV 55%) h. A single-dose morphine 100 mcg·kg(-1) achieved a mean CMAX 10 mcg·l(-1) . Repeat 4-hourly dosing achieved mean steady-state concentration 13-18 mcg·l(-1) ; concentrations associated with good analgesia after intravenous administration. Serum concentration variability was large ranging from 5 to 55 mcg·l(-1) at steady state. CONCLUSIONS: Oral morphine 200 mcg·kg(-1) then 100 mcg·kg(-1) 4 h or 150 mcg·kg(-1) 6 h achieves mean concentrations associated with analgesia. There was high serum concentration variability suggesting that respiration may be compromised in some children given these doses. |
en |
dc.publisher |
Blackwell Publishing Inc. |
en |
dc.relation.ispartofseries |
Pediatric Anesthesia |
en |
dc.rights |
Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. |
en |
dc.rights.uri |
https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm |
en |
dc.title |
Oral morphine dosing predictions based on single dose in healthy children undergoing surgery |
en |
dc.type |
Journal Article |
en |
dc.identifier.doi |
10.1111/pan.13020 |
en |
pubs.issue |
1 |
en |
pubs.begin-page |
28 |
en |
pubs.volume |
27 |
en |
dc.rights.holder |
Copyright: Blackwell Publishing Inc. |
en |
dc.identifier.pmid |
27779356 |
en |
pubs.end-page |
36 |
en |
pubs.publication-status |
Published |
en |
dc.rights.accessrights |
http://purl.org/eprint/accessRights/RestrictedAccess |
en |
pubs.subtype |
Article |
en |
pubs.elements-id |
544203 |
en |
pubs.org-id |
Medical and Health Sciences |
en |
pubs.org-id |
Medical Sciences |
en |
pubs.org-id |
Pharmacology |
en |
pubs.org-id |
School of Medicine |
en |
pubs.org-id |
Anaesthesiology |
en |
dc.identifier.eissn |
1460-9592 |
en |
pubs.record-created-at-source-date |
2017-03-09 |
en |
pubs.online-publication-date |
2016-10-25 |
en |
pubs.dimensions-id |
27779356 |
en |