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Can anyone explain the following observation:
After administration of an IV bolus of morphine (5 mg/kg) in rats,
immediately from the first blood sample taken at 5 minutes, plasma
concentrations of the metabolite morphine-3-glucuronide (M3G) are higher
than plasma concentrations of morphine. When administering morphine as a
continuous IV infusion (10 mg/kg/h), M3G concentrations during the first 20
minutes of infusion are lower than morphine after which metabolite
concentrations exceed morphine concentrations. Does anyone has suggestions
to explain the different M3G/Morphine concentration ratio following bolus
administration and during the initial period of continuous infusion.
Many thanks,
Peter De Paepe, MD
Heymans Institute of Pharmacology
De Pintelaan 185
B-9000 Gent
Belgium
TEL : +32 (0)9 240 33 56
FAX : +32 (0)9 240 49 88
e-mail : peter.depaepe.at.rug.ac.be
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Dr.Paepe,
This observation could be at least partly explained by very
rapid metabolism of morphine to the M3G metabolite in rats. The
plasma concentrations following a bolus would decline rapidly
resulting in a rapid decrease in the ratio of parent drug to
metabolite, as the metabolite quickly accumulates after the
entire morphine dose has been given. In contrast, when given
as an infusion, the metabolite is formed less rapidly, and the
plasma concentrations of parent drug morphine tend to be maintained
as a function of infusion rate. In humans, drugs with short half-lives
are freqently given as continuous infusions so as to maintain
therapeutic plasma levels (eg dopamine, nitroglycerin, lidocaine).
Mike Leibold, PharmD, RPh
ML11439.at.goodnet.com
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