British Journal of Anaesthesia, Vol 77, Issue 6 764-772, Copyright © 1996 by The Board of Management and Trustees of the British Journal of Anaesthesia
R. N. Upton
A general model, based on indicator dilution principles, of the initial
distribution and effects of drugs in a target organ after i.v. bolus
administration is presented. The model was validated from previous studies
of myocardial pharmacokinetics and pharmacodynamics of lignocaine in sheep.
It is proposed that i.v. drug injection produces a concentration "peak" of
drug in venous blood, which is attenuated by vascular mixing, and lung and
heart kinetics, as the drug is transported from the injection site to the
heart where it exerts its effects. The model predicted that the first
passage of this peak through the heart was the principal component of
myocardial concentrations of lignocaine for 10 min after injection before
recirculation became important. Injection rate, cardiac output and
myocardial blood flow were important determinants of the magnitude of the
first pass peak. The model provides a physiological framework for analysing
the initial distribution of drugs.
LABORATORY INVESTIGATIONS
A model of the first pass passage of drugs from i.v. injection site to the heart--parameter estimates for lignocaine in the sheep
Department of Anaesthesia and Intensive Care, Royal Adelaide Hospital, University of Adelaide, North Terrace, Adelaide, SA 5005, Australia
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