title: Effects of furanocoumarins in Kampo extract-based medicines on rat intestinal absorption of CYP3A and P-glycoprotein substrate drugs in vivo.
abstract: While a great deal of information of drug-drug interactions is known, most concern Western drugs. Relatively little is known of the interactions between Western drugs and traditional drugs such as Kampo extract medicines (Japanese medicines modified from traditional Chinese medicines). This study investigated the effects of the marketed Kampo extract medicines, Senkyu-cha-cho-san and Sokei-kakketsu-to, on the intestinal absorption of CYP or P-glycoprotein (P-gp) in vivo. Midazolam, a CYP3A substrate drug, or talinolol, a P-gp substrate drug, was orally administered to rats with each of these Kampo extract medicines. Senkyu-cha-chosan or Sokei-kakketsu-to administered as a standard regimen did not obviously affect Cmax and area under the curve (AUC) of midazolam, although both Kampo extract medicines contained notopterol, a potent CYP3A4 inhibitor in vitro. The results implied a lack of potent drug-drug interactions between both Kampo extract medicines and CYP3A substrate drugs. Concomitant administration of each Kampo extract medicine unexpectedly showed the tendency to decrease Cmax and AUC of talinolol. Decreased intestinal absorption of talinolol might be caused, not by the inhibition of P-gp, but by the inhibition of organic anion transporting peptides by both Kampo extract medicines.
authors.affiliation: Division of Pharmaceutics, Osaka University of Pharmaceutical Sciences, Osaka 569-1094, Japan. iwanaga@gly.oups.ac.jp
authors.forename: Kazunori
authors.initials: K
authors.lastname: Iwanaga
authors.forename: Kaori
authors.initials: K
authors.lastname: Arimune
authors.forename: Makoto
authors.initials: M
authors.lastname: Miyazaki
authors.forename: Makio
authors.initials: M
authors.lastname: Shibano
authors.forename: Masahiko
authors.initials: M
authors.lastname: Taniguchi
authors.forename: Kimiye
authors.initials: K
authors.lastname: Baba
authors.forename: Masawo
authors.initials: M
authors.lastname: Kakemi
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000818:Animals; D019540:Area Under Curve; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D011564:Furocoumarins / Q000494:pharmacology*; D041743:Herb-Drug Interactions; D007408:Intestinal Absorption / Q000187:drug effects*; D007422:Intestines / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D020835:Medicine, Kampo; D008657:Metabolic Clearance Rate; D008874:Midazolam / Q000097:blood / Q000493:pharmacokinetics*; D011412:Propanolamines / Q000097:blood / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D004365:Drugs, Chinese Herbal; D011564:Furocoumarins; D011412:Propanolamines; C011550:talinolol; D051544:Cytochrome P-450 CYP3A; D008874:Midazolam