Pharmacokinetic interactions between Japanese traditional medicine (kampo) and modern medicine (III). Effect of Sho-seiryu-to on the pharmacokinetics of azelastine hydrochloride in rats.
Sho-seiryu-to (SST) is widely used herbal formula in Japanese traditional medicine (kampo) to treat allergic diseases. Since Japanese physicians frequently prescribe this formula combined with azelastine hydrochloride, one of anti-histamine and anti-allergic medicines, we evaluated the pharmacokinetic interactions between SST and azelastine hydrochloride in rats to obtain the drug information for the prevention from disadvantage or adverse effects by their combined therapy. Oral administration of SST did not influence the plasma concentration profile of azelastine after its intravaneous injection, suggesting that SST would not change the activities of metabolic enzymes such as cytochrome P450s. However, maximum concentration (C(max)) of azelastine after oral administration of azelastine hydrochloride was significantly reduced and mean residence time (MRT) was significantly lengthened when SST was orally administered at 20 times amount of human daily dosage. There was not significant difference in the area under the plasma concentration-time curve (AUC), suggesting that SST might delay the absorption of azelastine without affecting the extent of bioavailability. Since this delay was independent of ephedrine that is a main constituent of SST and that a suppressor for gastric transit, SST might form unsoluble complex with azelastine to reduce its absorption. At the double of human daily dose, SST did not made the absorption of azelastine delay. The possibility that SST reduce the absorption of azelastine hydrochloride could not be denied completely, however, it is suggested that SST would not cause pharmacokinetic interaction with azelastine hydrochloride clinically.
Makino
Toshiaki
T
Department of Kampo Medicinal Science, Hokkaido College of Pharmacy, Otaru, Japan. makino@hokuyakudai.ac.jp
Inagaki
Takahiro
T
Komatsu
Ken-Ichi
K
Kano
Yoshihiro
Y
D000818:Animals; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000493:pharmacokinetics*; D005260:Female; D020835:Medicine, Kampo; D010793:Phthalazines / Q000737:chemistry / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley
D004365:Drugs, Chinese Herbal; D010793:Phthalazines; C090832:sho-seiryu-to; C020976:azelastine