Pharmacokinetics of verproside after intravenous and oral administration in rats |
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Authors: | Eun Jeong Park Hyun Sook Lee Sei-Ryang Oh Hyeong-Kyu Lee Hye Suk Lee |
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Institution: | (1) National Research Laboratory for Drug Metabolism and Bioanalysis, College of Pharmacy, Wonkwang University, Iksan, 570-749, Korea;(2) Natural Medicines Research Center, Korea Research Institute of Biology & Biotechnology, Daejeon, 560-180, Korea;(3) Drug Metabolism & Bioanalysis Lab., College of Pharmacy, Wonkwang University, Shinyongdong, Iksan, 570-749, Korea |
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Abstract: | 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. |
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Keywords: | Verproside Isovanilloylcatalpol Pharmacokinetics Rats LC/MS |
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