title: Absence of drug interaction between Hwang-Ryun-Hae-Dok-Tang and phenolsulfonphthalein.
abstract: Hwang-Ryun-Hae-Dok-Tang (HT; a standardized herbal formula consisting of extracts from Coptidis Rhizoma, Scutellariae Radix, Phellodendri Cortex, and Gardeniae Fructus) was reported to modulate a function of multidrug resistance associated protein 2 (Mrp2) in vitro. The aim of this study was to assess the in vivo pharmacokinetic interactions between HT and phenolsulfonphthalein (PSP), a typical model Mrp2 substrate eliminated via bile through Mrp2 in rats. Rats received intravenous PSP (0.8 mg/kg) followed by either a single oral dose of HT (0.42 g/kg) or multiple oral doses of HT (0.42 g/kg for 7 days). The effect of HT treatment was also investigated at a steady-state after intravenous PSP infusion. In contrast to previous in vitro results, in this study, we found that the HT-treated and control groups did not show any significant difference in the plasma PSP concentration and pharmacokinetic parameters, including area under the plasma concentration-time curve (AUC; control: 118 ± 19, single dose: 116 ± 40, and multiple dose: 137 ± 4, in mg/(min·mL)) and biliary clearance (control: 3.15 ± 0.69, single dose: 2.59 ± 1.11, and multiple dose: 2.53 ± 0.65, in mL/(min·kg)). However, cyclosporine A (5 mg/kg, an inhibitor of Mrp2) significantly decreased the AUC and biliary clearance of PSP. The steady-state plasma concentration and biliary clearance of PSP-were also similar between the groups. Taken together, our results suggest that HT may not be affected by Mrp2-mediated herb-drug interaction in vivo.
authors.affiliation: College of Pharmacy, Kyung Hee University, Seoul 130-701, Korea.
authors.forename: Hong Jae
authors.initials: HJ
authors.lastname: Yi
authors.forename: Ju-Hee
authors.initials: JH
authors.lastname: Oh
authors.forename: Young-Joo
authors.initials: YJ
authors.lastname: Lee
mesh_terms: D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D001646:Bile / Q000187:drug effects / Q000378:metabolism; D004396:Coloring Agents / Q000378:metabolism* / Q000493:pharmacokinetics; D016572:Cyclosporine / Q000378:metabolism / Q000493:pharmacokinetics; D004347:Drug Interactions; D041743:Herb-Drug Interactions; D007262:Infusions, Intravenous; D008297:Male; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000378:metabolism; D010637:Phenolsulfonphthalein / Q000378:metabolism* / Q000493:pharmacokinetics; D010936:Plant Extracts / Q000378:metabolism* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D004396:Coloring Agents; D016572:Cyclosporine; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D010637:Phenolsulfonphthalein; D010936:Plant Extracts; C476904:hwangryunjihwang-tang