Absence of Drug Interaction Between Hwang-Ryun-Hae-Dok-Tang and Phenolsulfonphthalein

作者：Yi Hong Jae; Oh Ju Hee; Lee Young Joo^*

来源：Archives of Pharmacal Research, 2010, 33(12): 2025-2031.

DOI：10.1007/s12272-010-1219-9

• Herb-drug interaction
• Pharmacokinetics
• Hwang-Ryun-Hae-Dok-Tang
• Phenolsulfonphthalein
• Biliary excretion

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.

• 出版日期2010-12