Paclitaxel is one of the most frequently used
anticancer agents but its use is sometimes limited because of the incidence of severe
hypersensitivity reactions. The clinical symptoms of the reactions, including
dyspnea and
pulmonary edema, are similar to those induced by iodinated contrast medium during radiographic examination. Therefore, the
premedication for the prophylaxis of
hypersensitivity reactions to
paclitaxel is carried out in accordance with that for radiographic contrast medium. In the present study, we compared the effects of
paclitaxel and an iodinated radiocontrast medium
ioxaglate on vascular permeability and pulmonary function in rats. Both
paclitaxel (15 mg/kg) and
ioxaglate (4 g
iodine/kg) caused perivascular
edema, plasma extravasation and decrease in arterial PaO2.
Dexamethasone inhibited plasma extravasation induced by the two compounds. In contrast,
histamine H1 and H2 antagonists attenuated the effects of
ioxaglate without inhibiting those of
paclitaxel. On the other hand, a neurokinin NK1 antagonist (
LY303870: 0.5 mg/kg) significantly inhibited the pulmonary responses induced by
paclitaxel but not by
ioxaglate. Therefore, it is suggested that
paclitaxel and
ioxaglate cause similar
acute lung injury but the mechanisms are different between the two compounds, in which
histamine and
substance P are involved in the pulmonary dysfunction induced by
ioxaglate and
paclitaxel, respectively. These findings also raise a possibility that more effective
premedication is required for the prophylaxis of
paclitaxel hypersensitivity.