Background: The cardiovascular effects of halothane are well recognize
d, but little is known of how this affects drug distribution, The effe
ct of halothane anesthesia on physiologic factors that affect drug dis
position from the moment of injection was investigated, Methods: The d
ispositions of markers of intravascular space and blood flow (indocyan
ine green), extracellular space and free water diffusion (inulin), and
total body water and tissue perfusion (antipyrine) were determined in
four purpose-bred coonhounds. The dogs were studied while awake and w
hile anesthetized with 1%, 1.5%, and 2% halothane in a randomized orde
r determined by a repeated measures Latin square experimental design,
Marker dispositions were described by recirculatory pharmacokinetic mo
dels based on frequent early and less frequent later arterial blood sa
mples. These models characterize the role of cardiac output and its di
stribution on drug disposition. Results: Halothane caused a significan
t and dose-dependent decrease in cardiac output, The disposition of an
tipyrine was most profoundly affected by halothane anesthesia, which i
ncreased both nondistributive intercompartmental clearance and volume
while decreasing fast and slow tissue clearances and elimination clear
ance in a halothane dose-dependent manner, Conclusions: Halothane-indu
ced changes in blood flow to the compartments of the antipyrine recirc
ulatory model were not proportional to changes in cardiac output. Halo
thane anesthesia significantly increased (to more than double) the are
a under the drug concentration versus time curve due to an increase in
the apparent peripheral blood flow not involved in drug distribution,
despite a dose-dependent cardiac output decrease. Recirculatory pharm
acokinetic models include the best aspects of traditional compartmenta
l and physiologic pharmacokinetic models while offering advantages ove
r both.