Marked decrease of cyclosporin absorption caused by phellamurin in rats.
Phellamurin is a flavonoid glycoside that is abundant in the leaves of Phellodendron wilsonii Hayata et Kanehira (Rutaceae). In vitro everted rat intestine study indicated that phellamurin inhibited intestinal P-glycoprotein in a dose-dependent manner. In order to investigate the effect of phellamurin on cyclosporin absorption and disposition, rats were given cyclosporin (5 mg/kg) with or without phellamurin in a parallel design. Fluorescence polarization immunoassay was used to determine the blood concentration of cyclosporin. Unanticipatedly, our results indicated that the coadministration of phellamurin significantly decreased the Cmax of cyclosporin by 77 % and reduced the AUC(0-infinity) of cyclosporin by 56 %. This indicated that a serious interaction occurred between phellamurin with cyclosporin. To ensure the efficacy of cyclosporin, we suggest that the coadministration of phellamurin or Phellodendron wilsonii with cyclosporin should be avoided.
Chen
Hung-Yi
HY
Graduate Institute of Pharmaceutical Chemistry, China Medical College, Taichung, Taiwan, R.O.C.
Wu
Tian-Shung
TS
Su
Sheng-Fang
SF
Kuo
Sheng-Chu
SC
Chao
Pei-Dawn Lee
PD
D000818:Animals; D019540:Area Under Curve; D016572:Cyclosporine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004365:Drugs, Chinese Herbal; D005260:Female; D005419:Flavonoids / Q000097:blood / Q000737:chemistry / Q000494:pharmacology*; D007082:Ileum / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D007408:Intestinal Absorption / Q000187:drug effects; D007583:Jejunum / Q000187:drug effects* / Q000378:metabolism; D015394:Molecular Structure; D051381:Rats; D017207:Rats, Sprague-Dawley; D027821:Rutaceae
D004365:Drugs, Chinese Herbal; D005419:Flavonoids; C016043:phellamurin; D016572:Cyclosporine