Diamorphine pharmacokinetics and conversion factor estimates for intranasal diamorphine in paediatric breakthrough pain: systematic review
Diamorphine pharmacokinetics and conversion factor estimates for intranasal diamorphine in paediatric breakthrough pain: systematic review
Background: intranasal diamorphine is a potential treatment for breakthrough pain but few paediatric data are available to assist dose estimation.
Aim: ot determine an intranasal diamorphine dose in children through an understanding of pharmacokinetics.
Design: a systematic review of the literature was undertaken to seek diamorphine pharmacokinetic parameters in neonates, children and adults. Parenteral and enteral diamorphine bioavailability were reviewed with respect to formation of the major metabolite, morphine. Clinical data quantifying equianalgesic effects of diamorphine and morphine were reviewed.
Review sources: PubMed (1960-2020); EMBASE (1980-2020); IPA (1973-2020) and original human research studies that reported diacetylmorphine and metabolite after any dose or route of administration.
Results: the systematic review identified 19 studies: 16 in adults and 1 in children and 2 neonatal reports. Details of study participants were extracted. Age ranged from premature neonates to 67 years and weight 1.4-88 kg. Intranasal diamorphine bioavailability was predicted as 50%. The equianalgesic intravenous conversion ratio of morphine:diamorphine was 2:1. There was heterogeneity between pharmacokinetic parameter estimates attributed to routes of administration, lack of size standardisation, methodology and pharmacokinetic analysis. Estimates of the pharmacokinetic parameters clearance and volume of distribution were reduced in neonates. There were insufficient paediatric data to characterise clearance or volume maturation of either diamorphine or its metabolites.
Conclusions: we estimate equianalgesic ratios of intravenous morphine:diamorphine 2:1, intravenous morphine:intranasal diamorphine 1:1 and oral morphine:intranasal diamorphine of 1:3. These ratios are based on adult literature, but are reasonable for deciding on an initial dose of 0.1 mg/kg in children 4-13 years.
chronic conditions, clinical decisions, paediatrics, pain, pharmacology
Gastine, Silke
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Morse, James D.
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Leung, Miriam T.Y.
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Wong, Ian Chi Kei
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Howard, Richard F.
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Harrop, Emily
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Liossi, Christina
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Standing, Joseph F.
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Jassal, Satbir Singh
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Hain, Richard D.
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Skene, Simon
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Oulton, Kate
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Law, Siew L.
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Quek, Wan T.
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Anderson, Brian J.
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Gastine, Silke
718bb82b-3e82-432c-9807-848c22f5d4e6
Morse, James D.
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Leung, Miriam T.Y.
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Wong, Ian Chi Kei
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Howard, Richard F.
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Harrop, Emily
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Liossi, Christina
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Standing, Joseph F.
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Jassal, Satbir Singh
e202480b-9ec8-4f0d-b13b-1a85493c7e6d
Hain, Richard D.
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Skene, Simon
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Oulton, Kate
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Law, Siew L.
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Quek, Wan T.
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Anderson, Brian J.
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Gastine, Silke, Morse, James D., Leung, Miriam T.Y., Wong, Ian Chi Kei, Howard, Richard F., Harrop, Emily, Liossi, Christina, Standing, Joseph F., Jassal, Satbir Singh, Hain, Richard D., Skene, Simon, Oulton, Kate, Law, Siew L., Quek, Wan T. and Anderson, Brian J.
(2022)
Diamorphine pharmacokinetics and conversion factor estimates for intranasal diamorphine in paediatric breakthrough pain: systematic review.
BMJ Supportive & Palliative Care, [003461].
(doi:10.1136/bmjspcare-2021-003461).
Abstract
Background: intranasal diamorphine is a potential treatment for breakthrough pain but few paediatric data are available to assist dose estimation.
Aim: ot determine an intranasal diamorphine dose in children through an understanding of pharmacokinetics.
Design: a systematic review of the literature was undertaken to seek diamorphine pharmacokinetic parameters in neonates, children and adults. Parenteral and enteral diamorphine bioavailability were reviewed with respect to formation of the major metabolite, morphine. Clinical data quantifying equianalgesic effects of diamorphine and morphine were reviewed.
Review sources: PubMed (1960-2020); EMBASE (1980-2020); IPA (1973-2020) and original human research studies that reported diacetylmorphine and metabolite after any dose or route of administration.
Results: the systematic review identified 19 studies: 16 in adults and 1 in children and 2 neonatal reports. Details of study participants were extracted. Age ranged from premature neonates to 67 years and weight 1.4-88 kg. Intranasal diamorphine bioavailability was predicted as 50%. The equianalgesic intravenous conversion ratio of morphine:diamorphine was 2:1. There was heterogeneity between pharmacokinetic parameter estimates attributed to routes of administration, lack of size standardisation, methodology and pharmacokinetic analysis. Estimates of the pharmacokinetic parameters clearance and volume of distribution were reduced in neonates. There were insufficient paediatric data to characterise clearance or volume maturation of either diamorphine or its metabolites.
Conclusions: we estimate equianalgesic ratios of intravenous morphine:diamorphine 2:1, intravenous morphine:intranasal diamorphine 1:1 and oral morphine:intranasal diamorphine of 1:3. These ratios are based on adult literature, but are reasonable for deciding on an initial dose of 0.1 mg/kg in children 4-13 years.
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Diamorphine pharmacokinetics and conversion factor estimates for intranasal diamorphine in paediatric breakthrough pain
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Accepted/In Press date: 26 January 2022
e-pub ahead of print date: 19 February 2022
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Funding Information:
This paper presents independent research funded by the National Institute for Health Research (NIHR) under its Research for Patient Benefit (RfPB) Programme (Grant Reference Number PB-PG-0317–20036). The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care.
Funding Information:
Professor Ian Wong is the founder of Therakind Ltd which was funded by Wockhardt Pharmaceutical to conduct the clinical studies for Ayendi® (diamorphine hydrochloride) licensing application.
Publisher Copyright:
© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.
Keywords:
chronic conditions, clinical decisions, paediatrics, pain, pharmacology
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Local EPrints ID: 482966
URI: http://eprints.soton.ac.uk/id/eprint/482966
ISSN: 2045-435X
PURE UUID: c93d6a1a-ce4e-4020-bf0e-57db9a43adaa
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Date deposited: 17 Oct 2023 17:01
Last modified: 17 Mar 2024 03:04
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Contributors
Author:
Silke Gastine
Author:
James D. Morse
Author:
Miriam T.Y. Leung
Author:
Ian Chi Kei Wong
Author:
Richard F. Howard
Author:
Emily Harrop
Author:
Joseph F. Standing
Author:
Satbir Singh Jassal
Author:
Richard D. Hain
Author:
Simon Skene
Author:
Kate Oulton
Author:
Siew L. Law
Author:
Wan T. Quek
Author:
Brian J. Anderson
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