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https://hdl.handle.net/2440/35679
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Type: | Journal article |
Title: | Population pharmacokinetic modelling of subcutaneous morphine in the elderly |
Author: | Upton, R. Semple, T. Macintyre, P. Foster, D. |
Citation: | Acute Pain, 2006; 8(3):109-116 |
Publisher: | Elsevier BV |
Issue Date: | 2006 |
ISSN: | 1366-0071 |
Abstract: | Background: The sources of variability in the blood concentrations of morphine after subcutaneous administration are unclear. Methods: A population pharmacokinetic model (using NONMEM) was used to examine data on morphine disposition following its administration (5 mg) via an indwelling s.c. cannula to elderly post-operative patients. Results: A two-compartment model with first order absorption was preferred. The between subject variability (BSV) was between 45 and 95% for the systemic parameters, and 71% for the absorption rate constant. The rate of subcutaneous absorption of morphine was not inherently more variable than other factors affecting morphine disposition. A sensitivity analysis supported these findings. In eight patients who received a second dose of morphine approximately 300 min after the first dose, the between occasion variability (BOV) of the parameters was up to 81% of the total variability. Conclusions: A significant component of the variability in morphine disposition was due to factors that could alter within a patient between doses. Taken together, this reinforces the need to titrate the dose of morphine to clinical endpoints, and questions the concept of a fixed dose for a given patient over time, especially if given at fixed dose intervals (i.e. on a time-contingent basis). © 2006 Elsevier B.V. All rights reserved. |
DOI: | 10.1016/j.acpain.2006.06.002 |
Published version: | http://dx.doi.org/10.1016/j.acpain.2006.06.002 |
Appears in Collections: | Anaesthesia and Intensive Care publications Aurora harvest 6 |
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