Cytochrome P450 isoforms contribution, plasma protein binding, toxicokinetics of enniatin A in rats and in vivo clearance prediction in humans

被引：7

作者：

Bhateria, Manisha ^{[1
,2
]}

Karsauliya, Kajal ^{[1
,2
]}

Sonker, Ashish Kumar ^{[1
,2
,3
]}

Yahavi, C. ^{[1
,2
,3
]}

Singh, Sheelendra Pratap ^{[1
,2
,3
]}

机构：

[1] CSIR Indian Inst Toxicol Res CSIR IITR, Regulatory Toxicol Grp, Toxicokinet Lab, Analyt Chem Lab, Lucknow, Uttar Pradesh, India

[2] CSIR Indian Inst Toxicol Res CSIR IITR, Food Drug & Chem Toxicol Grp, Lucknow, Uttar Pradesh, India

[3] Acad Sci & Innovat Res AcSIR, Ghaziabad, India

来源：

FOOD AND CHEMICAL TOXICOLOGY | 2022年 / 164卷

关键词：

Enniatin A; Emerging mycotoxins; Metabolism; Toxicokinetics; UPLC-MS/MS; EMERGING FUSARIUM-MYCOTOXINS; ABSOLUTE ORAL BIOAVAILABILITY; DRUG-METABOLISM; VITRO METABOLISM; QUANTITATIVE-DETERMINATION; HUMAN PHARMACOKINETICS; INTRINSIC CLEARANCE; UNCERTAINTY FACTORS; HUMAN VARIABILITY; BEAUVERICIN;

D O I：

10.1016/j.fct.2022.112988

中图分类号：

TS2 [食品工业];

学科分类号：

0832 ;

摘要：

Emerging mycotoxins, such as enniatin A (ENNA), are becoming a worldwide concern owing to their presence in different types of food and feed. However, comprehensive toxicokinetic data that links intake, exposure and toxicological effects of ENNA has not been elucidated yet. Therefore, the present study investigated the in vitro (rat and human) and in vivo (rat) toxicokinetic properties of ENNA. Towards this, an easily applicable and sensitive bioanalytical method was developed and validated for the estimation of ENNA in rat plasma. ENNA exhibited high plasma protein binding (99%), high hepatic clearance and mainly underwent metabolism via CYP3A4 (74%). The in-house predicted hepatic clearance (54 mL/min/kg) and observed in vivo rat clearance (55 mL/min/kg) were comparable. The predicted in vivo human hepatic clearance was 18 mL/min/kg. ENNA underwent slow absorption (T-max = 4 h) and rapid elimination following oral administration to rats. The absolute oral bioavailability was 47%. The toxicokinetic findings for ENNA from this study will help in designing and interpreting toxicological studies in rats. Besides, these findings could be used in physiologically based toxicokinetic (PBTK) model development for exposure predictions and risk assessment for ENNA in humans.

引用

页数：10

共 93 条

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