Fentanyl and propofol uptake by the lung: effect of time between injections.

The effect of time between the administrations of fentanyl and propofol on the first pass uptake of propofol in the cat lung was studied using double indicator dilution technique. The pulmonary first pass uptake of propofol (mean +/- s.e. mean) was 58 +/- 6% in six cats (control group) that had received no fentanyl prior to propofol (1 mg/kg) administration. The uptake was significantly reduced to 32 +/- 3% in animals pretreated with fentanyl (1 microgram/kg) 30 seconds before propofol administration (n = 6). However, when fentanyl was administered 3 minutes (n = 6) or 10 minutes (n = 6) prior to propofol, the pulmonary uptake of propofol (45 +/- 5%, 50 +/- 7% respectively) was not significantly reduced. The results demonstrate that the ability of fentanyl to inhibit pulmonary removal of propofol depends on its time of administration prior to propofol. These data may have clinical implication with respect to timing of the preinduction opiate injection.

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.