Abstract

Iced teas (ITs), also known as ready-to-drink teas, have gained much popularity among many nations. The modulatory effect of tea beverages on CYP3A4 increases the possibility of their potential interactions with many coadministered medications. Being a substrate of CYP3A4, sorafenib (SOR), the first-line therapy for the treatment of hepatocellular carcinoma, shows a great probability to exhibit pharmacokinetic (PK) interaction with ITs. For this purpose, different groups of Wistar rats were given oral doses of SOR (40 mg/kg), along with different types of ITs. The concentration of SOR in rat plasma was determined using UPLC-MS/MS. Chromatographic analysis was performed on a C18 analytical column, Acquity UPLC BEH™ (100 × 1.0 mm, i.d., 1.7 μm particle size), using erlotinib (ERL) as an internal standard. Isocratic elution was performed with a mobile phase consisting of two solvents: solvent A (water with 0.1% formic acid) and solvent B (acetonitrile with 0.1% formic acid), in a ratio of 30 : 70, v/v, respectively. Quantitation was performed using MRM of the transitions from protonated precursor ions [M+H]+ to product ions at m/z 465.12 > 252.02 (SOR) and m/z 394.29 > 278.19 (ERL). The method was fully validated as per the FDA guidance for bioanalytical method validation in the concentration range of 2.5–500 ng/mL. Different PK parameters were calculated for SOR in all rat groups and groups administered with ITs and SOR, compared with groups with simply water and SOR. Experimental data revealed that ITs caused a general reduction in SOR bioavailability; an approximate reduction of 30% was recorded for all types of tested ITs. These data indicate that ITs could affect the PK profile of SOR in rats.

Highlights

  • Cytochrome P450 enzymes (CYP 450) are the most important drug-metabolizing enzymes (DMEs) which are responsible for the detoxification of most drug substances

  • Green tea (GT), black tea (BT), and white tea (WT) are all obtained from Camellia sinensis plant. ey only differ in the manufacturing process and in their content of flavonoids known as catechins [3] which are known for their anticancer effect [4, 5]

  • Practical experimentation revealed that the protonated precursor ion [M+H]+ was detected at m/z 465.12 (SOR) and 394.29 (ERL, internal standard (IS)). e product ion spectra (Figure 1) of SOR/ERL showed major fragments at m/z 252.02 (SOR) and 278.19 (ERL)

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Summary

Introduction

Cytochrome P450 enzymes (CYP 450) are the most important drug-metabolizing enzymes (DMEs) which are responsible for the detoxification of most drug substances. Drugs and daily consumed food products and beverages can affect the enzymatic activity by either inducing or inhibiting CYPs. A plethora of studies have focused on discussing the issue of drug-drug interactions between different therapeutic agents and to a lesser extent between food/beverage products and coadministered drugs [1,2,3]. Tea is considered the most popular consumed beverage which comes second to water. Ey only differ in the manufacturing process and in their content of flavonoids known as catechins [3] which are known for their anticancer effect [4, 5]. Iced teas (ITs), known as readyto-drink teas, have gained much popularity among many

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