Use of a limited physiologic model to explain target organ toxicity of bupivacaine as a function of route of administration.
A physiologic model to describe bupivacaine uptake by and elimination from brain and heart was developed. Preliminary validation of the model was accomplished by comparing concentration data predicted by the model with those determined in rabbits. The model was modified to examine similarities and differences following intravenous and epidural administration of 150 mg of bupivacaine in humans. Simulations illustrated why rapid cardiovascular and central nervous system toxicity occurs following intravenous administration and is absent when an identical dose is administered epidurally. A slow continuous intravenous infusion of bupivacaine was simulated to examine the possibility that brain and heart concentrations would continue to accumulate reaching toxic concentrations in the absence of blood concentrations associated with bupivacaine toxicity.
D D
DD
Denson
G A
GA
Thompson
D E
DE
Coyle
D000818:Animals; D001921:Brain / Q000378:metabolism*; D002045:Bupivacaine / Q000008:administration & dosage / Q000378:metabolism* / Q000633:toxicity; D002560:Cerebrovascular Circulation; D003326:Coronary Circulation; D006801:Humans; D007275:Injections, Intravenous; D007700:Kinetics; D008433:Mathematics; D008954:Models, Biological; D009206:Myocardium / Q000378:metabolism*; D011817:Rabbits; D013045:Species Specificity
D002045:Bupivacaine