Pharmacokinetics of verproside after intravenous and oral administration in rats

• Published in: Archives of pharmacal research 2009, 32(4), , pp.559-564
• Main Authors: Park, Eun Jeong, Lee, Hyun Sook, Oh, Sei-Ryang, Lee, Hyeong-Kyu, Lee, Hye Suk
• Format: Article
• Language: English
• Subjects: Administration, Oral; Animals; Anti-Asthmatic Agents - administration & dosage; Anti-Asthmatic Agents - pharmacokinetics; Biological Availability; Biotransformation; Dose-Response Relationship, Drug; Drug Stability; Glucosides - administration & dosage; Glucosides - pharmacokinetics; Hydrogen-Ion Concentration; Injections, Intravenous; Iridoid Glucosides; Iridoids - administration & dosage; Iridoids - pharmacokinetics; Male; Medicine; Microsomes, Liver - metabolism; Pharmacology/Toxicology; Pharmacy; Rats; Rats, Sprague-Dawley; 약학
• ISSN: 0253-6269; 1976-3786
• DOI: 10.1007/s12272-009-1412-x

Verproside, a catalpol derivative iridoid glucoside isolated from Pseudolysimachion longifolium , is a candidate for anti-asthmatic drug. The dose-dependency of the pharmacokinetics of verproside was evaluated in rats after intravenous and oral administration. After intravenous administration of verproside (2, 5 and 10 mg/kg doses), the systemic clearance ( Cl ) was significantly reduced and AUC was significantly increased at 10 mg/kg dose compared to 2 and 5 mg/kg doses. The volume of distribution at steady state ( V ss ) remained unchanged as the dose was increased. The extent of urinary excretion was low for both intravenous (3.3–6.2%) and oral (0.01–0.04%) doses. Isovanilloylcatalpol was identified as a metabolite after intravenous administration of verproside and showed the significant decreases in AUC and C max at 10 mg/kg verproside dose. The reduced systemic clearance of verproside at high doses appears to be due to the saturable metabolism. Upon oral administration of verproside (20, 50 and 100 mg/kg doses), C max was nonlinearly increased. The extent of verproside recovered from the gastrointestinal tract at 24 h after oral administration was 0.01–0.72% for all three doses studied. The absolute oral bioavailability ( F ) was 0.3 and 0.5% for 50 and 100 mg/kg doses, respectively. Low F appears to be due to first-pass metabolism.