The role of OATP1B1 and OATP1B3 transporter polymorphisms in drug disposition and response to anticancer drugs: a review of the recent literature

Anabtawi, Nadeen; Drabison, Thomas; Hu, Shuiying; Sparreboom, Alex; Talebi, Zahra

doi:10.1080/17425255.2022.2113380

Cited by 12 publications

(3 citation statements)

References 101 publications

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“…OATPs mediate the transport of various exogenous and endogenous substances independently of sodium and ATP (7,11). Genetic variations can result in drug plasma concentrations varying by up to 600 times in individuals with the same body weight receiving the same standard dose and are a major contributor to the signi cant interindividual variability in therapeutic response and toxicity observed in the majority of patient populations (12). Of the 199 individuals with hepatitis C in our study, 53 (26.6%) experienced adverse effects.…”

Section: Dıscussıonmentioning

confidence: 74%

The Impact of OATP Variants on the Side Effects of Direct-Acting Antivirals in Hepatitis C Patients

ALTINTAŞ,

ALTINTAŞ

2024

Preprint

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Background: Organic anion-transporting polypeptides (OATPs) are responsible for the cellular uptake of a broad range of endogenous compounds and xenobiotics in multiple tissues. The aim of our study was to determine whether variations in OATP1B1 and OATP1B3 affect the side effects experienced by hepatitis C patients treated with direct-acting antivirals (DAAs). Methods: This study included 199 hepatitis C patients treated with DAAs. ledipasvir (LDV)/sofosbuvir (SOF) or ombitasvir (OBV)/paritaprevir (PTV)/ritonavir (RTV)+/-dasabuvir (DSV) (PrOD) and 162 control individuals without hepatitis C. Treatment-related side effects were recorded. The OATP1B1 gene variations c.388A>G and c.521T>C and the OATP1B3 gene variations c.334T>G and c.699G>A were analyzed via the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Results: Side effects were observed in 53 (26.6%) of 199 hepatitis C patients. There were skin lesions in 19 patients (9.5%), fatigue in 18 patients (9%), pruritus in 11 patients (5.5%), and nausea in 5 patients (2.5%). There was a significant relationship between the c.334T>G variant and side effects (p=0.001 for all). A significant relationship was found between the OATP1B1 c.521T/c.388A allele and between the OATP1B3 c.699A/c.334T allele and side effects (p=0.010, p=0.042, respectively). The frequency distribution of the c.334T>G variant was in Hardy–Weinberg equilibrium. The frequencies of the patient group and the control group were 65.3% and 63%, respectively. Conclusion: We found a relationship between the c.334T>G variant in OATP1B3 and DAA-related side effects in hepatitis C patients.

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Section: Dıscussıonmentioning

confidence: 74%

The Impact of OATP Variants on the Side Effects of Direct-Acting Antivirals in Hepatitis C Patients

ALTINTAŞ,

ALTINTAŞ

2024

Preprint

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“…Levothyroxine is mainly degraded in the liver and is a substrate for both OATP1B1 and OATP1B3, potentially leading to lower liver uptake and slower elimination of these contrast agents. , Hormonal therapy may also impact the hepatic elimination of contrast agents. Estrogens including estrone sulfate, 17β-estradiol, and estradiol sulfate are among OATP1B1’s known endogenous and exogenous substrates, which, following their metabolism, are transported out of hepatocytes by efflux transporters such as MRP2 . Although these substances may produce drug–drug interactions with gadoxetate and gadobenate in women, there are no studies that investigate potential increases in contrast agents exposure in patients under thyroid or hormonal therapy.…”

Section: Eliminationmentioning

confidence: 99%

Gender Differences in Pharmacokinetics: A Perspective on Contrast Agents

Courchesne,

Manrique,

Bernier

et al. 2023

ACS Pharmacol. Transl. Sci.

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Gender is an important risk factor for adverse drug reactions. Women report significantly more adverse drug reactions than men. There is a growing consensus that gender differences in drug PK is a main contributor to higher drug toxicity in women. These differences stem from physiological differences (body composition, plasma protein concentrations, and liver and kidney function), drug interactions, and comorbidities. Contrast agents are widely used to enhance diagnostic performance in computed tomography and magnetic resonance imaging. Despite their broad use, these contrast agents can lead to important adverse reactions including hypersensitivity reactions, nephropathy, and hyperthyroidism. Importantly, female gender is one of the main risk factors for contrast agent toxicity. As these adverse reactions may be related to gender differences in PK, this perspective aims to describe distribution and elimination pathways of commonly used contrast agents and to critically discuss gender differences in these processes.

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“…OATP1B3 is one of the organic anion-transporting polypeptides, which could mediate the uptake of small anion molecules in cells. [26,27] Recent studies showed that OATP1B3 was involved in the cellular uptake of ICG fluorescent dye, indicating OATP1B3 is a potential reporter gene for near-infrared fluorescence molecular imaging. Therefore, we speculated that a miRNA-inducible OATP1B3 switch system (miR-ON-OB3) is promising for nearinfrared fluorescence imaging of miRNA.…”

Section: Construction and Validation Of A Mirna-inducible Oatp1b3 Switchmentioning

confidence: 99%

Near‐Infrared Fluorescence Imaging of miRNA Using a Transmembrane Polypeptide‐Based Genetic Reporter

Shu,

Ma,

Tian

et al. 2023

Small Methods

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MicroRNAs (miRNAs) are small noncoding RNAs that play important regulatory roles in multiple biological processes. Many miRNAs exhibit unique expression patterns and are considered as theranostic biomarkers in a variety of human diseases. A reporter system that is capable of imaging miRNA in vivo is crucial for investigating miRNA biology. In the present study, an organic anion‐transporting polypeptide 1B3 (OATP1B3)‐based genetic switch system is designed and optimized to achieve near‐infrared fluorescent imaging of miRNA by the uptake of indocyanine green (ICG) dye. The reporter system, named miR‐ON‐OB3, is shown to be efficient to regulate the expression of OATP1B3 in mammalian cells. Notably, the results indicate that the system is of high sensitivity for near‐infrared fluorescence imaging of both exogenous and endogenous miRNA in mammalian cells. Moreover, the system is proved to be functional for real‐time near‐infrared fluorescence imaging of miRNA in living mice. This study establishes a novel genetic encoded reporter for near‐infrared fluorescence imaging of miRNA, which may provide a potential tool for in vivo imaging of miRNA in clinical applications due to the clinical availability of ICG.

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The role of OATP1B1 and OATP1B3 transporter polymorphisms in drug disposition and response to anticancer drugs: a review of the recent literature

Cited by 12 publications

References 101 publications

The Impact of OATP Variants on the Side Effects of Direct-Acting Antivirals in Hepatitis C Patients

The Impact of OATP Variants on the Side Effects of Direct-Acting Antivirals in Hepatitis C Patients

Gender Differences in Pharmacokinetics: A Perspective on Contrast Agents

Near‐Infrared Fluorescence Imaging of miRNA Using a Transmembrane Polypeptide‐Based Genetic Reporter

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