Influence of mefenamic acid on the intestinal absorption and metabolism of three bioactive flavones in Radix Scutellariae and potential pharmacological impact

Abstract

Context: Mefenamic acid (MEF) and the dried root of Scutellaria baicalensis Georgi (Radix Scutellariae, RS) share a high possibility of combined medication to treat inflammation. Objective: The present study investigates the impact of MEF on absorption/disposition of three major components in RS (baicalein, B; wogonin, W; oroxylin A, OA) and further pharmacological changes. Materials and methods: The apparent permeability (Papp) and percentage of metabolism of B, W and OA at 10μ were measured at the absence/presence of MEF (100μ) in the Caco-2 cell monolayer model. A modified whole blood assay was employed to quantify prostaglandin E2 (PGE2) 4, 6 and 8h post-oral administration with water suspension of MEF at 40mg/kg and RS at 200mg/kg. Results: In the presence of MEF, Papp of B, W and OA were increased from 1.69±0.89×10 -6, 1.57±0.10×10-6 and 3.09±0. 70×10-6cm/sec to 5.24±0.27×10-6, 6.08±0.19×10-6 and 4.13±0.38×10 -6, whereas their percentage of metabolism was decreased from 72.75±2.44%, 73.27±3.25% and 89.84±2.99% to 21.11±0.69%, 17.90±5.55% and 45.44±3.38%. PGE2 level was much lower in the co-administration group (49.04±2.03pg/ml) than in the MEF group (73.13±3.03pg/ml) or RS group (494.37±11.75pg/ml) 4h post MEF dosing, suggesting a synergic effect. Discussion and conclusion: Co-administration of MEF and RS could induce potential alterations in their pharmacokinetic profiles and anti-inflammatory effects. © 2014 Informa Healthcare USA, Inc. All rights reserved.