Permeability and transport mechanism of trihexyphenidyl hydrochloride in Caco-2 cell monolayer model with a validated UPLC-MS/MS method

Lu, Chengcan; Fu, Kejia; Cao, Kangna; Wei, Jiali; Zhou, Jing; Zhao, Di; Li, Ning; Lu, Yang; Chen, Xijing; Zhang, Yongjie

doi:10.1016/j.jpba.2019.112924

Cited by 11 publications

(4 citation statements)

References 34 publications

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“…Caco-2 cells were cultured in Dulbecco’s modified Eagle’s medium (DMEM; GIBCO, Carlsbad, CA, USA) supplemented with 10% fetal bovine serum (GIBCO), 1% nonessential amino acid solution, and antibiotics (100 U/mL penicillin and 100 g/mL streptomycin from GIBCO) with a minor modification according to Lu [ 40 ]. Cells were grown in an incubator with 5% CO 2 and 95% humidity at 37 °C, with medium replaced every 2–3 days.…”

Section: Methodsmentioning

confidence: 99%

Hydroxylated Tetramethoxyflavone Affects Intestinal Cell Permeability and Inhibits Cytochrome P450 Enzymes

Jan,

Gavahian

2024

Molecules

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Tetramethoxyflavones (TMFs) found in the Citrus genus have garnered considerable interest from food scientists and the health food industry because of their promising biological properties. Nonetheless, there are currently limited data available regarding the effectiveness and bioavailability of “hydroxylated TMFs”, which are flavones known for their potential in disease prevention through dietary means. This study aims to provide insights into the chemical and biological properties of hydroxylated TMF and evaluates its effects on intestinal cell permeability and cytochrome P450 (CYP) inhibition. Liquid chromatography–mass spectrometry (LC-MS) and microsomes analyze the TMFs and hydroxylated TMFs, elucidating cell penetration and metabolic inhibition potential. 3H7-TMF shows the fastest (1-h) transport efficiency in intestinal cells. The Caco-2 cell model exhibits significant transport and absorption efficiency. Dissolved hydroxyl-TMF with hydrophilicity possibly permeates the gut. 3H7-TMF has higher transport efficiency (46%) 3H6-TMF (39%). IC50 values of TMFs (78-TMF, 57-TMF, 3H7-TMF, 3H6-TMF) against CYP enzymes (CYP1A2, CYP2D6, CYP2C9, CYP2C19, CYP3A4) range from 0.15 to 108 μM, indicating potent inhibition. Hydroxyl groups enhance TMF hydrophilicity and membrane permeability. TMFs display varied inhibitory effects due to hydroxyl and methoxy hindrance. This study underscores the strong CYP inhibitory capabilities in these TMFs, implying potential food–drug interactions if used in medicines or supplements. These findings can also help with food nutrition improvement and pharma food developments through innovative approaches for Citrus waste valorization.

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Section: Methodsmentioning

confidence: 99%

Hydroxylated Tetramethoxyflavone Affects Intestinal Cell Permeability and Inhibits Cytochrome P450 Enzymes

Jan,

Gavahian

2024

Molecules

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“…Although, historically radiolabelling techniques were used. Lu et al [73], recently reported the validation of an ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) to quantify the amount and consequent intestinal permeability of the anticholinergic drug, Trihexyphenidyl hydrochloride, in caco-2 cells. The study successfully validated the method and in addition, gained information on the transport mechanism of that specific drug.…”

Section: In Vitro Methodsmentioning

confidence: 99%

Role of MALDI-MSI in combination with 3D tissue models for early stage efficacy and safety testing of drugs and toxicants

Spencer

Flint

Duckett

et al. 2020

Expert Review of Proteomics

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“…The Caco-2 cell line was derived from human colon adenocarcinoma and its morphology and function are similar to those of human intestinal epithelial cells, and it contains enzymes related to the brush border epithelium of small intestine [24]. Caco-2 cell model has been widely used in the study of drug uptake, efflux, transmembrane transport and other absorption mechanisms at home and abroad in the past decade because of its good correlation, reproducibility and applicability with oral drug absorption in intestinal tract [25][26][27][28][29].…”

Section: Introductionmentioning

confidence: 99%

Elucidation of the Transport Mechanism of Puerarin and Gastrodin and Their Interaction on the Absorption in a Caco-2 Cell Monolayer Model

Jiang

Xiong

et al. 2022

Molecules

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Puerarin (PUR) and gastrodin (GAS) are often used in combined way for treating diseases caused by microcirculation disorders. The current study aimed to investigate the absorption and transportation mechanism of PUR and GAS and their interaction via Caco-2 monolayer cell model. In this work, the concentration in Caco-2 cell of PUR and GAS was determined by HPLC method. The bidirectional transport of PUR and GAS and the inhibition of drug efflux including verapamil and cyclosporine on the transport of these two components were studied. The mutual influence between PUR and GAS, especially the effect of the latter on the former of the bidirectional transport were also investigated. The transport of 50 μg·mL−1 PUR in Caco-2 cells has no obvious directionality. While the transport of 100 and 200 μg·mL−1 PUR presents a strong directionality, and this directionality can be inhibited by verapamil and cyclosporine. When PUR and GAS were used in combination, GAS could increase the absorption of PUR while PUR had no obvious influence on GAS. Therefore, the compatibility of PUR and GAS is reasonable, and GAS can promote the transmembrane transport of PUR, the effect of which is similar to that of verapamil.

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Permeability and transport mechanism of trihexyphenidyl hydrochloride in Caco-2 cell monolayer model with a validated UPLC-MS/MS method

Cited by 11 publications

References 34 publications

Hydroxylated Tetramethoxyflavone Affects Intestinal Cell Permeability and Inhibits Cytochrome P450 Enzymes

Hydroxylated Tetramethoxyflavone Affects Intestinal Cell Permeability and Inhibits Cytochrome P450 Enzymes

Role of MALDI-MSI in combination with 3D tissue models for early stage efficacy and safety testing of drugs and toxicants

Elucidation of the Transport Mechanism of Puerarin and Gastrodin and Their Interaction on the Absorption in a Caco-2 Cell Monolayer Model

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