Modulation of Cytochrome P450 Activity by 18β‐Glycyrrhetic Acid and its Consequence on Buspirone Pharmacokinetics in Rats. (23rd May 2015)

• Record Type: Journal Article
• Authors: Kim, Sang‐Bum; Cho, Hyun‐Jong; Kim, Yeong Shik; Kim, Dae‐Duk; Yoon, In‐Soo
• Is Part Of: Phytotherapy research. Volume 29:Number 8(2015:Aug.)
• Page Start: 1188
• Page End: 1194
• Publication Date: 2015-05-23
• Subjects: Materia medica, Vegetable -- Periodicals; Botany, Medical -- Periodicals; Medicinal plants -- Periodicals; Plant Extracts -- therapeutic use -- Periodicals; Plants, Medicinal -- Periodicals; 581.634
• DOI: 10.1002/ptr.5365
• Languages: English
• ISSNs: 0951-418X

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>The aim of this study was to elucidate the inhibition mechanism of 18β‐glycyrrhetic acid (GLY) on cytochrome P450 (CYP) activity and <italic>in vivo</italic> pharmacokinetic consequences of single GLY dose in rats. An <italic>in vitro</italic> CYP inhibition study in rat liver microsomes (RLM) was conducted using probe substrates for CYPs. Then, an <italic>in vivo</italic> pharmacokinetics of intravenous and oral buspirone (BUS), a probe substrate for CYP3A, was studied with the concurrent administration of oral GLY in rats. In the <italic>in vitro</italic> CYP inhibition study, CYP3A was involved in the metabolism of GLY. Moreover, GLY inhibited CYP3A activity with an IC<sub>50</sub> of 20.1 ± 10.7 μM <italic>via</italic> a mixed inhibition mechanism. In the <italic>in vivo</italic> rat pharmacokinetic study, single oral GLY dose enhanced the area under plasma concentration–time curve (AUC) of intravenous and oral BUS, but the extent of increase in AUC was only minimal (1.12–1.45 fold). These results indicate that GLY can inhibit the <italic>in vitro</italic> CYP3A‐mediated drug metabolism in RLM <italic>via</italic> a mixed inhibition mechanism. However, the impact of single oral GLY dose on the pharmacokinetics of BUS in rats was limited, showing that GLY could function as merely a weak inhibitor for CYP3A‐mediated drug metabolism <italic>in vivo</italic>. Copyright © 2015 John Wiley & Sons, Ltd.</p> </abstract>