Pharmacokinetics of verproside after intravenous and oral administration in rats.
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.
Park
Eun Jeong
EJ
National Research Laboratory for Drug Metabolism and Bioanalysis, College of Pharmacy, Wonkwang University, Iksan, 570-749, Korea.
Lee
Hyun Sook
HS
Oh
Sei-Ryang
SR
Lee
Hyeong-Kyu
HK
Lee
Hye Suk
HS
D000284:Administration, Oral; D000818:Animals; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D001682:Biological Availability; D001711:Biotransformation; D004305:Dose-Response Relationship, Drug; D004355:Drug Stability; D005960:Glucosides / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D006863:Hydrogen-Ion Concentration; D007275:Injections, Intravenous; D057888:Iridoid Glucosides; D039823:Iridoids / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D018927:Anti-Asthmatic Agents; D005960:Glucosides; D057888:Iridoid Glucosides; D039823:Iridoids; C512483:verproside