Pulmonary uptake of propofol in cats. Effect of fentanyl and halothane.
BACKGROUND
Many drugs are removed by the lung. The pulmonary uptake of one drug can be inhibited when a second, highly accumulated drug is administered parenterally or as a chronic oral treatment. The effect of inhalational anesthetics on pulmonary drug uptake has not been extensively studied and may alter pharmacokinetics of intravenously administered drugs.


METHODS
The uptake of propofol by the lung during a single passage through the pulmonary circulation was studied in four groups 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 with 1% (n = 6) or 1.5% (n = 6) halothane. In an additional group, the single-pass pulmonary uptake of propofol was studied in six spontaneously breathing cats pretreated with fentanyl. The amount of propofol taken up by the lung during the first pass was measured from double indicator-dilution outflow curves using indocyanine green (ICG) as the intravascular reference indicator.


RESULTS
The first-pass uptake of propofol (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 ventilated, respectively. Although exposure of the animals to 1% halothane had 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 mechanical ventilation of the lungs without exposure to halothane. Also, in animals pretreated with fentanyl, propofol uptake was reduced to 40 +/- 5% compared with the control group.


CONCLUSIONS
The results demonstrate 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-drug interaction that may interfere with the pharmacokinetic profile of propofol, and may alter the amount of propofol needed to achieve or supplement a given depth of anesthesia.
Department of Anesthesia, University of Pennsylvania, Philadelphia 19104-4283.
I
I
Matot
C F
CF
Neely
R Y
RY
Katz
G R
GR
Neufeld
D000769:Anesthesia, Inhalation; D000771:Anesthesia, Intravenous; D000818:Animals; D002415:Cats; D005283:Fentanyl / Q000494:pharmacology*; D006221:Halothane / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D015742:Propofol / Q000493:pharmacokinetics*; D012121:Respiration, Artificial
D005283:Fentanyl; D006221:Halothane; D015742:Propofol