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Diamorphine pharmacokinetics and conversion factor estimates for intranasal diamorphine in paediatric breakthrough pain:systematic review

Gastine, Silke; Morse, James D; Leung, Miriam Ty; Wong, Ian Chi Kei; Howard, Richard F; Harrop, Emily; Liossi, Christina; ... Anderson, Brian J; + view all (2022) Diamorphine pharmacokinetics and conversion factor estimates for intranasal diamorphine in paediatric breakthrough pain:systematic review. BMJ Supportive and Palliative Care 10.1136/bmjspcare-2021-003461. (In press). Green open access

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Abstract

BACKGROUND: Intranasal diamorphine is a potential treatment for breakthrough pain but few paediatric data are available to assist dose estimation. AIM: To 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.

Type: Article
Title: Diamorphine pharmacokinetics and conversion factor estimates for intranasal diamorphine in paediatric breakthrough pain:systematic review
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1136/bmjspcare-2021-003461
Publisher version: https://doi.org/10.1136/bmjspcare-2021-003461
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: chronic conditions, clinical decisions, paediatrics, pain, pharmacology
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Infection, Immunity and Inflammation Dept
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Practice and Policy
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy
URI: https://discovery.ucl.ac.uk/id/eprint/10144280
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