Abstract
Acute vaso-occlusive painful episodes associated with sickle cell disease (SCD) are
frequently treated with morphine. Many SCD individuals require relatively higher doses
of morphine to achieve optimal analgesia. We studied pharmacokinetics of morphine
in SCD to explore if altered disposition could be a factor contributing to increased
requirement of morphine in this population. The study subjects were in steady state
of health to avoid the effect of hemodynamic changes associated with vaso-occlusion
on morphine disposition. The plasma concentrations of morphine and its major metabolites
were measured at timed intervals in 21 SCD subjects after they received a single .1 mg/Kg
infusion of morphine sulfate. USCPACK software was used to fit candidate pharmacokinetic
models. Noncompartmental pharmacokinetic parameters for morphine were calculated.
Morphine clearance was 2.4–3.6 L/h, half-life was .3–.7 hours, AUC0-∞ was 27.7–42.5 ng∗h/mL, and volume of distribution was .96–3.38 L/kg. Clearance of
morphine in the study population was 3–10 folds higher than published estimates in
the non-SCD population, with correspondingly lower AUC and half-life. Volume of distribution
was similar. This observation suggests that due to increased clearance SCD individuals
may require higher dose and frequency of morphine to achieve comparable plasma levels.
Perspective
Accelerated clearance of morphine likely related to increased hepatic and renal blood
flow may be responsible for increased requirement of morphine in SCD. Although SCD
individuals may require higher and more frequent doses of morphine, inter-individual
variability of morphine disposition highlights the importance of individualization
of the therapy.
Key words
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Article info
Publication history
Published online: January 31, 2011
Accepted:
October 26,
2010
Received in revised form:
September 15,
2010
Received:
July 7,
2010
Footnotes
Supported by Grants No. K12RR17613 (D.D.), 1K24RR19729 (J.A.), MO1-RR10284 (HU GCRC) from the National Center for Research Resources, and K23AI076106 (MN) from the National Institute of Allergy and Infectious Diseases.
None of the authors had any conflict related to this report.
Identification
Copyright
© 2011 American Pain Society. Published by Elsevier Inc. All rights reserved.
