Effects of Kampo medicines on P-glycoprotein.
The Kampo medicines are more and more often used in recent years, usually together with the western drugs. The need for the investigation of drug interactions between Kampo medicines and western drugs are, therefore, widely recognized. Among the various possible causes for the drug-drug interactions, those related to pharmacokinetics such as drug metabolism and transport are regarded as most frequent and clinically important. In the present study, the effects of Kampo medicines on the P-glycoprotein (P-gp), one of the major drug transporters, were investigated in in vitro studies using human P-gp membranes. The P-gp activity in the presence and absence of commonly used 50 Kampo medicines was evaluated by the ATPase assay detecting the inorganic phosphate produced by the ATP hydrolysis. The ATPase activity was inhibited by most of the Kampo medicines studied, indicating the possibility of their inhibiting the P-gp. The degree of inhibition in the presence of verapamil, a P-gp substrate, showed a significant correlation with that in the absence of verapamil. Furthermore, the inhibitory effect of the Kampo medicines on the ATPase activity correlated with their licorice root (kanzo) content, suggesting the contribution of licorice root in the P-gp inhibition. Because licorice root is one of the most common ingredients in the Kampo medicines and is also often used in the food as a sweetener, it might be necessary to pay attention on the interaction between the licorice root-containing drug/food and the number of drugs transported by P-gp.
Satoh
Toshiyuki
T
Department of Clinical Pharmacokinetics, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan.
Watanabe
Yuka
Y
Ikarashi
Nobutomo
N
Ito
Kiyomi
K
Sugiyama
Kiyoshi
K
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors*; D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors*; D000255:Adenosine Triphosphate / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects; D006035:Glycyrrhiza; D041743:Herb-Drug Interactions; D029001:Herbal Medicine; D006801:Humans; D006868:Hydrolysis; D020835:Medicine, Kampo; D010710:Phosphates; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology*; D018517:Plant Roots; D014700:Verapamil / Q000494:pharmacology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002121:Calcium Channel Blockers; D010710:Phosphates; D010936:Plant Extracts; D000255:Adenosine Triphosphate; D014700:Verapamil; D000251:Adenosine Triphosphatases