Assessment of the genotoxic effects of antihypertensive drug active ingredient indapamide in human lymphocytes

Avuloğlu-Yılmaz, Ece; Yüzbaşıoğlu, Deniz; Ünal, Fatma

doi:10.1080/01480545.2022.2026375

Cited by 2 publications

(4 citation statements)

References 28 publications

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“…The results of the statistical analysis of our study coincided with those recorded in the public assessment report of indapamide [16]. The results of SNPs rs7438135, and rs11740316, indicated a non-significant difference between the pharmacokinetic parameters of indapamide across the three tested genotypes GG (wild-type), AG (Heterozygous), and AA (Homozygous).…”

Section: Discussionsupporting

confidence: 85%

“…Seventeen blood samples were collected from the volunteers at the fasting condition at the following time intervals; 0 (directly before dosing), 1,2,3,4,6,8,10,12,14,16,18,20,24,36,48, and 72 h after dosing. On the other hand, eighteen blood samples were collected for the fed state at 0 (directly before dosing), 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 14, 16, 24, 36, 48, and 72 h after dosing.…”

Section: Study Proceduresmentioning

confidence: 99%

“…Chlorthalidone and indapamide have been found to reduce cardiovascular events, compared to hydrochlorothiazide alone, which showed no evidence of lowering cardiovascular events [15]. Regarding indapamide safety, an in vitro study showed that indapamide had no considerable genotoxic impact on human lymphocytes [16]. Moreover, long-term indapamide therapy, typically in combination with perindopril, showed indications of benefit in terms of mortality and morbidity [17].…”

Section: Introductionmentioning

confidence: 99%

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Association between Food/UGT2B7 Polymorphisms and Pharmacokinetics/Pharmacodynamics Properties of Indapamide in Healthy Humans

2023

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Indapamide is an effective and safe antihypertensive medication showing a beneficial effect in combination with other antihypertensive agents regarding morbidity and mortality. A comparative study was performed under fasting and fed conditions to investigate the effect of food and selected single nucleotide polymorphisms in the uridine diphosphate glucuronyl transferase (UGT2B7) gene on the pharmacokinetics and pharmacodynamics behavior of indapamide 1.5 mg sustained release. Forty-nine healthy volunteers aged 18–55 years were randomized into two groups; 25 volunteers were administered indapamide under fasting conditions and 24 under fed conditions. Genotyping of the UGT2B7 rs7438135 and rs11740316 was done before commencing the study using predesigned TaqMan assays. Results showed that food independently decreased the value of indapamide’ Tmax by 5.5 h and increased the value of Cmax by 8.7 ng/mL. On the other hand, all genetic variants of both UGT2B7 SNPs had no significant impact on the values of Tmax, Cmax, and AUC0–t; however, it was found that rs11740316 variant AG was correlated with a 2.8 h lower MRTinf. Finally, BMI positively correlated with longer MRTinf. It was concluded that none of rs7438135, rs11740316, or food had a significant impact on the pharmacodynamic properties. Food had a modest impact on indapamide Cmax and Tmax values, while there were unremarkable differences in safety and efficacy.

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Section: Discussionsupporting

confidence: 85%

Section: Study Proceduresmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Association between Food/UGT2B7 Polymorphisms and Pharmacokinetics/Pharmacodynamics Properties of Indapamide in Healthy Humans

2023

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“…The genotoxicity of chemicals can also be determined by the sister chromatid exchanges (SCEs) assay which is a simple and rapid method that indicates the genetic material exchange at homologous loci during the S phase of the cell cycle (Akbaş et al, 2022; Avuloglu‐Yilmaz et al, 2022; Yilmaz et al, 2015). SCE formation is associated with the recombinational repair, as well as point mutations, gene amplifications, and cytotoxicity (Cobanoglu & Cayir, 2021).…”

Section: Genotoxicity Testsmentioning

confidence: 99%

Cellular toxicities of gadolinium‐based contrast agents used in magnetic resonance imaging

Akbas

Ünal

Yüzbaşıoğlu

2022

J of Applied Toxicology

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Contrast agents have been used in magnetic resonance imaging (MRI) as a radiological method. Gadolinium‐based contrast agents (GBCAs), because of their paramagnetic characteristics, are the ones mostly used in MRI to increase signal intensity. However, the use of contrast media has raised concerns on cellular toxic risks of these agents. Studies showed the accumulation of gadolinium after injection to humans with or without renal impairment. Also, there are findings obtained under in vitro and/or in vivo conditions that revealed conflicting results for their cytotoxic and genotoxic effects. Some of them declared damage in cells and genetic material; some others did not. Abnormal cell growth and genetic aberration are critical because they may lead to carcinogenesis in somatic cells or may be transferred to the next generations through germ cells. Therefore, understanding the effect of GBCAs on cells is important for their safer usage in clinical administrations to generate high‐quality contrast‐enhanced magnetic resonance images. Because of all these reasons, cellular toxicities—mainly genotoxic and cytotoxic effects—of GBCAs were reviewed in this paper.

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Assessment of the genotoxic effects of antihypertensive drug active ingredient indapamide in human lymphocytes

Cited by 2 publications

References 28 publications

Association between Food/UGT2B7 Polymorphisms and Pharmacokinetics/Pharmacodynamics Properties of Indapamide in Healthy Humans

Association between Food/UGT2B7 Polymorphisms and Pharmacokinetics/Pharmacodynamics Properties of Indapamide in Healthy Humans

Cellular toxicities of gadolinium‐based contrast agents used in magnetic resonance imaging

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