Evaluation of First‐Pass Cytochrome P4503A (CYP3A) and P‐glycoprotein Activities Using Felodipine and Hesperetin in Combination in Wistar Rats and Everted Rat Gut Sacs in Vitro

• Published in: Phytotherapy research 2014-05, Vol.28 (5), p.699-705
• Main Authors: Sridhar, V, Surya Sandeep, M, Ravindra Babu, P, Naveen Babu, K
• Format: Article
• Language: English
• Subjects: Administration, Oral; Animals; ATP Binding Cassette Transporter, Sub-Family B - metabolism; Biological Transport; blood; CYP3A4; Cytochrome P-450 CYP3A - metabolism; dihydropyridines; felodipine; Felodipine - blood; Felodipine - pharmacokinetics; flavanones; Half-Life; hesperetin; Hesperidin - pharmacology; Ileum - drug effects; Ileum - metabolism; in vitro studies; In Vitro Techniques; intestinal absorption; Intestinal Absorption - drug effects; liver; Male; oral administration; P-glycoprotein; pharmacokinetics; Rats; Rats, Wistar; Verapamil - pharmacology
• ISSN: 0951-418X; 1099-1573
• DOI: 10.1002/ptr.5040

The effects of hesperetin on the pharmacokinetics and the role of P‐glycoprotein (P‐gp) in the transport of felodipine were investigated in rats and in vitro. Felodipine was administered orally (10 mg/kg) without or with hesperetin (25, 50 and 100 mg/kg) to rats for 15 consecutive days. Blood samples were collected at different time intervals on 1ˢᵗ day in single dose pharmacokinetic study (SDS) and on 15ᵗʰ day in multiple dose pharmacokinetic study (MDS). The area under the plasma concentration–time curve (AUC₀–∞) and the peak plasma concentration (Cₘₐₓ) of felodipine were dose‐dependently increased in SDS and MDS with hesperetin compared to control ( p