Andrographolide, which is one of the main pharmaceutical ingredients in traditional Chinese medicine Andrographis paniculata, can clear heat, detoxify human body, cool blood and reduce swelling, etc. Respiratory tract infectious diseases have been treated with the combination of andrographolide and theophyllines clinically. As andrographolide inhibits the CYP1A2 activity in vitro, it potentially interacts with theophyllines that are mainly metabolized by CYP1A2. Therefore, we herein studied the effects of andrographolide on the pharmacokinetics of aminophylline and doxofylline in rats. The blood drug concentrations of aminophylline, doxofylline and its metabolite theophylline were determined by HPLC. The theophylline AUC(0-t) was significantly elevated confronting the combination of andrographolide and aminophylline compared to that of the control group (P<0.05). Meanwhile, when only aminophylline was used, the theophylline clearance rate was significantly higher than those in the case of combination (P<0.05). The pharmacokinetics parameters of doxofylline and its metabolite theophylline in the individual administration group showed no significantly different from that combined with andrographolide. The results suggest that andrographolide and aminophylline should not be simultaneously administered because the former may raise the risks of side effects by inhibiting the clearance of the latter. In contrast, it is more secure to combine doxofylline with andrographolide owing to the almost intact pharmacokinetics. © Georg Thieme Verlag KG Stuttgart · New York.