Background. Many drugs are removed by the lung. The pulmonary uptake o
f one drug can be inhibited when a second, highly accumulated drug is
administered parenterally or as a chronic oral treatment. The effect o
f inhalational anesthetics on pulmonary drug uptake has not been exten
sively studied and may alter pharmacokinetics of intravenously adminis
tered drugs. Methods: The uptake of propofol by the lung during a sing
le passage through the pulmonary circulation was studied in four group
s of anesthetized cats: spontaneously breathing cats (control group, n
= 6), cats whose lungs were mechanically ventilated (n = 6), and cats
whose lungs were mechanically ventilated and that were anesthetized w
ith 1% (n = 6) or 1.5% (n = 6) halothane. In an additional group, the
single-pass pulmonary uptake of propofol was studied in six spontaneou
sly breathing cats pretreated with fentanyl. The amount of propofol ta
ken up by the lung during the first pass was measured from double indi
cator-dilution outflow curves using indocyanine green (ICG) as the int
ravascular reference indicator. Results. The first-pass uptake of prop
ofol (mean +/- SEM) was 61.3 +/- 4.9% and 60 +/- 3.7% of the injected
dose in control cats and in cats whose lungs were mechanically ventila
ted, respectively. Although exposure of the animals to 1% halothane ha
d no significant effect on pulmonary extraction of propofol, the first
-pass uptake decreased significantly to 38.8 +/- 6.9% in cats exposed
to 1.5% halothane compared with control cats and to cats undergoing me
chanical ventilation of the lungs without exposure to halothane. Also,
in animals pretreated with fentanyl, propofol uptake was reduced to 4
0 +/- 5% compared with the control group. Conclusions. The results dem
onstrate a substantial extraction of propofol by the lung that is not
affected by mechanical ventilation. Inhibition of propofol uptake by 1
.5% halothane and by fentanyl provides a potential mechanism of drug-d
rug interaction that may interfere with the pharmacokinetic profile of
propofol, and may alter the amount of propofol needed to achieve or s
upplement a given depth of anesthesia.