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Kinetics of high‐dose intravenous morphine in cardiac surgery patients
Author(s) -
Stanski Donald R.,
Greenblatt David J.,
Lappas Demetrios G.,
Weser Jan Koch,
Lowenstein Edward
Publication year - 1976
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1002/cpt1976196752
Subject(s) - pharmacokinetics , volume of distribution , morphine , chemistry , distribution (mathematics) , distribution volume , anesthesia , elimination rate constant , compartment (ship) , blood volume , pharmacology , medicine , mathematical analysis , oceanography , mathematics , geology
Ten patients received 1.0 mg/kg of morphine sulfate by constant‐rate intravenous infusion at 5 mg/min over 9 to 27 min. Multiple arterial blood samples were drawn during the first 30 to 151 min after termination of the infusion, prior to institution of cardiopulmonary bypass. Postinfusion plasma concentrations were fitted by computer to biexponential functions consistent with a 2‐compartment open pharmacokinetic model. Mean (±SE) pharmacokinetic parameters were: volume ofcentral compartment, 0.09 ± 0.03 L/kg; total apparent volume of distribution, 1.02 ± 0.09 L/kg; distribution T½, 0.90 ± 0.09 min; apparent elimination T½, 137 ± 14 min; total clearance, 378 ± 63 ml/min. Thus distribution of morphine is very rapid, but the apparent volume of distribution is only slightly larger than body weight, suggesting limited tissue uptake. Since apparent elimination T½ are similar to those reported after smaller doses, evidence of saturable or capacity‐limited elimination is lacking. Total clearances, representing mainly hepatic clearance, averaged about 25% of hepatic blood flow, suggesting clinically important first‐pass metabolism of oral morphine.