PULMONARY UPTAKE OF PROPOFOL IN CATS - EFFECT OF FENTANYL AND HALOTHANE

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.