Morphine, morphine-6-glucuronide and morphine-3-glucuronide pharmacokinetics in newborn infants receiving diamorphine infusions

Barrett, D.A., Barker, D.P., Rutter, N., Pawula, M. and Shaw, P.N. (1996) Morphine, morphine-6-glucuronide and morphine-3-glucuronide pharmacokinetics in newborn infants receiving diamorphine infusions. British Journal of Clinical Pharmacology, 41 6: 531-537. doi:10.1046/j.1365-2125.1996.03539.x


Author Barrett, D.A.
Barker, D.P.
Rutter, N.
Pawula, M.
Shaw, P.N.
Title Morphine, morphine-6-glucuronide and morphine-3-glucuronide pharmacokinetics in newborn infants receiving diamorphine infusions
Journal name British Journal of Clinical Pharmacology   Check publisher's open access policy
ISSN 0306-5251
1365-2125
Publication date 1996-06
Sub-type Article (original research)
DOI 10.1046/j.1365-2125.1996.03539.x
Volume 41
Issue 6
Start page 531
End page 537
Total pages 7
Place of publication Oxford, United Kingdom
Publisher Wiley-Blackwell Publishing
Language eng
Formatted abstract
1. The pharmacokinetics of morphine, morphine-6-glucuronide (M6G) and morphine-3-glucuronide (M3G) were studied in 19 ventilated newborn infants (24-41 weeks gestation) who were given a loading dose of 50 μg kg-1 or 200 μg kg-1 of diamorphine followed by an intravenous infusion of 15 μg kg-1 h-1 of diamorphine. Plasma concentrations of morphine, M3G and M6G were measured during the accrual to steady-state and at steady state of the diamorphine infusion.

2. Following both the 50 μg kg-1 or 200 μg kg-1 loading doses the mean steady-state plasma concentration (±s.d.) of morphine, M3G and M6G were 86 ± 52 ng ml-1, 703 ± 400 ng ml-1 and 48 ± 28 ng ml-1 respectively and morphine clearance was found to be 4.6 ± 3.2 ml min-1 kg-1.

3. M3G formation clearance was estimated to be 2.5 ± 1.8 ml min-1 kg-1, and the formation clearance of M6G was estimated to be 0.46 ± 0.32 ml min-1 kg-1.

4. M3G metabolite clearance was 0.46 ± 0.60 ml min-1 kg-1, the elimination half-life was 11.1 ± 11.3 h and the volume of distribution was 0.55 ± 1.13 l kg-1. M6G metabolite clearance was 0.71 ± 0.36 ml min-1 kg-1, the elimination half-life was 18.2 ± 13.6 h and the volume of distribution was 1.03 ± 0.88 l kg-1.

5. No significant effect of the loading dose (50 μg kg-1 or 200 μg kg-1) on the plasma morphine or metabolite concentrations or their derived pharmacokinetic parameters was found.

6. We were unable to identify correlations between gestational age of the infants and any of the determined pharmacokinetic parameters.

7. M3G: morphine and M6G: morphine steady-state plasma concentration ratios were 11.0 ± 10.8 and 0.8 ± 0.8, respectively. 8. The metabolism of morphine in neonates, in terms of the respective contributions of each glucuronide pathway, was similar to that in adults.
Keyword Diamorphine
Morphine
Morphine-6-glucuronide
Morphine-3-glucoronide
Pharmacokinetics
Metabolism
Premature Newborn
Intravenous Infusion
Dose Regimen
Metabolites
Glucuronides
Volunteers
Alfentanil
Children
Heroin
Plasma
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ
Additional Notes Article first published online: 2 October 2003.

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Pharmacy Publications
 
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Created: Mon, 20 Dec 2010, 14:03:39 EST