Pharmacodynamic and pharmacokinetic studies of anthraquinone 2-carboxylic acid on passive cutaneous anaphylaxis in rats.

The objectives of this study are to describe the inhibitory effect of 9,10-anthraquinone 2-carboxylic acid (AQCA) on IgE-mediated passive cutaneous anaphylaxis (PCA) reaction, and the pharmacokinetics of AQCA. Pharmacodynamic assessments were performed at 0.5, 1 and 2 mg/kg (i.v.) and 5, 10 and 20 mg/kg (p.o) dose levels. In separate groups, pharmacokinetics were assessed at 5 mg/kg (i.v.) and 5, 10, and 20 mg/kg (p.o.) dose levels. Intravenous and oral administration of AQCA inhibited the PCA reaction in rats in a dose-dependent manner. The PCA-inhibitory activity of AQCA (20 mg/kg) lasted more than 12 hrs after oral administration. The oral bio-availability decreased with increasing dosage, from 96% (5 mg/kg) to 81% (10 and 20 mg/kg). The absorption after oral administration was prolonged with Tmax values ranging from 1 to 6 h; while t(1/2) (4.8-16 h) values appeared to be comparable. These results suggest that AQCA has a potent and long acting anti-PCA activity. It is likely to be therapeutically useful in the treatment of asthma.