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.
Cheng
H H
HH
Graduate Institute of Pharmaceutical Chemistry, China Medical College Taichung, Taiwan, ROC.
Kuo
S C
SC
Lin
W C
WC
D000284:Administration, Oral; D000818:Animals; D000880:Anthraquinones / Q000008:administration & dosage / Q000097:blood* / Q000494:pharmacology*; D019540:Area Under Curve; D002264:Carboxylic Acids / Q000008:administration & dosage / Q000097:blood* / Q000494:pharmacology*; D005260:Female; D006207:Half-Life; D007262:Infusions, Intravenous; D010323:Passive Cutaneous Anaphylaxis / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000880:Anthraquinones; D002264:Carboxylic Acids; C085798:9,10-anthraquinone 2-carboxylic acid