title: Influence of capsaicin on fluctuation of digoxin pharmacokinetics in lipopolysaccharide-treated rats.
abstract: In the present study, we investigated the influence of Cap on digoxin pharmacokinetics in lipopolysaccharide (LPS)-treated rats.        After the oral administration of digoxin (0.1 mg/kg), the area under the plasma concentration-time curve (AUC) of digoxin increased significantly until day 3 after LPS treatment. In the LPS + Cap group, the recovery period of AUC was shortened to 3 days. On days 5 and 7, the maximum plasma concentrations decreased significantly as compared to the control group. The bioavailability of digoxin in LPS group was higher than that in the LPS + Cap group.        The hepatic cytochrome P450 (CYP) 3A2 content decreased significantly until day 5 after LPS administration, but it returned to the control level until 5 days in the LPS + Cap group. Hepatic CYP3A2 mRNA expression of LPS group decreased significantly until day 3, but it returned to the control level on day 3 and increased significantly until day 7 in the LPS + Cap group.        The DNA-binding activity of pregnane X receptor (PXR) was increased on days 3-7 in the Cap and LPS + Cap group.        Cap decreased the absorption of digoxin by inducing CYP3A2 mRNA expression via indirect activation of PXR in LPS-treated rats.
authors.affiliation: Clinical Pharmacy and Clinical Pharmacokinetics, Osaka University of Pharmaceutical Sciences, Nasahara, Takatsuki, Osaka, Japan.
authors.forename: Ryuji
authors.initials: R
authors.lastname: Kato
authors.forename: Akina
authors.initials: A
authors.lastname: Higashitani
authors.forename: Takako
authors.initials: T
authors.lastname: Irie
authors.forename: Yugo
authors.initials: Y
authors.lastname: Kusukawa
authors.forename: Yu
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: Machiko
authors.initials: M
authors.lastname: Nakagawa
authors.forename: Yoko
authors.initials: Y
authors.lastname: Urashima
authors.forename: Makoto
authors.initials: M
authors.lastname: Nagata
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Hayashi
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Ijiri
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Tanaka
mesh_terms: D000284:Administration, Oral; D000818:Animals; D015153:Blotting, Western; D002211:Capsaicin / Q000008:administration & dosage / Q000494:pharmacology*; D051544:Cytochrome P-450 CYP3A; D004247:DNA / Q000378:metabolism; D004077:Digoxin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D024202:Electrophoretic Mobility Shift Assay; D005786:Gene Expression Regulation / Q000187:drug effects; D007275:Injections, Intravenous; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D000077297:Pregnane X Receptor; D011485:Protein Binding / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D011987:Receptors, Steroid / Q000378:metabolism
chemical_list: D008070:Lipopolysaccharides; D000077297:Pregnane X Receptor; D012333:RNA, Messenger; D011987:Receptors, Steroid; D004077:Digoxin; D004247:DNA; D051544:Cytochrome P-450 CYP3A; D002211:Capsaicin