Acute Pain
Volume 8, Issue 3 , Pages 109-116, October 2006

Population pharmacokinetic modelling of subcutaneous morphine in the elderly

  • R.N. Upton

      Affiliations

    • Department of Anaesthesia and Intensive Care, Royal Adelaide Hospital and University of Adelaide, North Terrace, Adelaide, SA 5000, Australia
    • Corresponding Author InformationCorresponding author. Tel.: +61 8 8303 6382; fax: +61 8 8303 3909.
    • ,
  • T.J. Semple

      Affiliations

    • Department of Anaesthesia and Intensive Care, Royal Adelaide Hospital and University of Adelaide, North Terrace, Adelaide, SA 5000, Australia
    • ,
  • P.E. Macintyre

      Affiliations

    • Department of Anaesthesia and Intensive Care, Royal Adelaide Hospital and University of Adelaide, North Terrace, Adelaide, SA 5000, Australia
    • ,
  • D.J.R. Foster

      Affiliations

    • School of Pharmacy, University of South Australia, Adelaide, SA 5000, Australia

Received 31 March 2006; received in revised form 24 May 2006; accepted 19 June 2006.

Summary 

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 (5mg) 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 300min 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).

Keywords: Morphine, Subcutaneous, Elderly, Population modelling, Between occasion variability

To access this article, please choose from the options below

Login to an existing account or Register a new account.

  • Purchase this article for 31.50 USD (You must login/register to purchase this article)

    Online access for 24 hours. The PDF version can be downloaded as your permanent record.

  • Visit SciVerse ScienceDirect to see if you have access via your institution.
 

PII: S1366-0071(06)00038-6

doi:10.1016/j.acpain.2006.06.002

Acute Pain
Volume 8, Issue 3 , Pages 109-116, October 2006

Article Tools

* Image Usage & Resolution