Influence of CYP2C9 Genetic Polymorphisms on the Pharmacokinetics of Losartan and Its Active Metabolite E-3174: A Systematic Review and Meta-Analysis

Park, Yoon-A; Song, Yuan‐Zong; Yee, Jeong; Yoon, Ha-Young; Gwak, Hye Sun

doi:10.3390/jpm11070617

Cited by 13 publications

(8 citation statements)

References 32 publications

(39 reference statements)

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“…For example, losartan is biotransformed into its active metabolite, EXP-3174, mediated by the metabolizing enzyme, CYP2C9 . A relationship between CYP2C9 polymorphisms and the pharmacokinetics of ARBs have also been observed, although the clinical impact in terms of BP was modest ( 20 ). It has been shown that AGTR1 mediates the function of ARBs by association with G proteins that activate a phosphatidylinositol-calcium second messenger system ( 21 ).…”

Section: Discussionmentioning

confidence: 99%

Personalized antihypertensive treatment guided by pharmacogenomics in China

Xiao¹,

Yang²,

Chen³

et al. 2022

Cardiovasc Diagn Ther

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Background: The implementation of genotyping for anti-hypertensive drugs in clinical practice remains a challenge. We conducted this study to analyze the distribution of polymorphisms of antihypertensive drugrelated genes in Changsha County in China and compare the clinical effectiveness of genotype-guided and clinical experience-guided antihypertensive therapy in hypertensive individuals.Methods: A total of 9,933 essential hypertensive participants from Changsha County were consecutively enrolled in our study, and 7 genetic polymorphic loci (CYP2D6*10, ADRB1, CYP2C9*3, AGTR1, ACE, CYP3A5*3 and NPPA) were detected by a polymerase chain reaction (PCR)-fluorescence probe. From an available sample of 660 hypertensive participants, 495 cases were randomly identified by genotype-guided therapy and 165 cases by clinical experience-guided therapy. We performed 24-hour ambulatory blood pressure (BP) monitoring on each of these cases, pre-and post-intervention.Results: In the enrolled 9,933 cases, the mutation frequencies of CYP2C9*3, ADRB1(1165G>C), AGTR1(1166A>C), CYP2D6*10, ACE(I/D), CYP3A5*3 and NPPA(2238T>C) were 4.41%, 74.60%, 5.55%, 57.08%, 30.94%, 69.03% and 1.19%, respectively. In both genotype-guided and clinical experience-guided groups, the comparisons of intra-group pre-and post-treatments showed significant decreases in diastolic blood pressure (DBP) (P<0.01) and significant increases in the control rate of BP (47.1% vs. 38.6% and 37.5% vs. 33.9%, P<0.05) in response to adjusted antihypertensive agents. Correspondingly, the extent of the reduction of systolic blood pressure (SBP; 3.52±11.72 vs. 0.92±9.14 mmHg), the extent of the increase in the rate of BP control (8.5% vs. 3.6%) and the percentage rate of decrease of grades 2 and 3 hypertensive individuals were more significant in the genotype-guided group than that in the clinical experience-guided group (P<0.01).Conclusions: While prescribing anti-hypertensive drugs, appropriate dosage and type adjustments should be made according to the gene mutation frequency and individual circumstances. Pharmacogenomics-guided personalized treatment of hypertensive patients is likely to be a more effective strategy, especially in those with significantly elevated SBP.

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Section: Discussionmentioning

confidence: 99%

Personalized antihypertensive treatment guided by pharmacogenomics in China

Xiao¹,

Yang²,

Chen³

et al. 2022

Cardiovasc Diagn Ther

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“…As for the metabolism of β blockers, anti-hypersensitive drugs, anti-arrhythmic drugs, and anti-depressants will not stop by AGP 2 as it does not inhibit CYP2D6 (Taylor et al 2020). AGP 2 also does not inhibit CYP2C9 which results in the metabolism of anti-clotting agents, anti-hypersensitive, anti-hypertensive, management of Type II Diabetes and Nonsteroidal Anti-Inflammatory (NSAIDs) (Park et al 2021). The CYP3A4 was not inhibited by AGP 2, which caused the oxidation of fatty acids, steroids, xenobiotics, and hormone synthesis (Samuels and Sevrioukova 2021).…”

Section: Adme Prediction Analysismentioning

confidence: 99%

In Silico Analysis of 14-Deoxy 11, 12-Didehydro Andrographolide (AGP 2) from Sambiloto (Andrographis paniculata) as Drug Candidate Against SARS-CoV-2

et al. 2023

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The outbreak of the COVID-19 pandemic in the world has urged researchers to develop a vaccine or therapeutic drugs to fight this virus. This study aimed to assay 14 deoxy-11,12-didehydroandrographolide (AGP 2) ability as an inhibitor of 3-chymotrypsin like-protease (3CLPro), Papain-like protease (PLPro), and RNA-dependent RNA-polymerase (RdRp), the viral proteins of SARS-CoV-2 and to evaluate it safeness as a drug candidate. In-silico technique was performed in this study to analyze the binding interaction, complex stability between protein and ligand, and drug-likeness properties. The proteins and ligands were obtained from Protein Data Bank (PDB) and PubChem web tools, then using PyRx to identify the binding affinity score, PyMoL to visualize the 3D binding interaction, and WebGro web tools to analyze the stability of each complex. A drug-likeness evaluation was done using SwissADME, pkCSM, and Way2drug web tools. The result of this study showed that the binding affinity score for each complex is; AGP 2-3CLPro (-6.7 kcal/mol), AGP 2- PLPro (-6.4 kcal/mol), and AGP 2-RdRp (-7.0 kcal/mol) where the AGP 2-RdRp and AGP 2-3CLPro showed a stable form indicating the inhibitor ability of AGP 2. This study also demonstrates that the drug-likeness properties of AGP 2 are safe to use. Additionally, it has been proved that AGP 2 can be developed into a therapeutic drug with further studies.

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“…They can selectively block the binding of angiotensin II in vascular smooth muscle and adrenal gland to its receptor subtype AT1, thus blocking the vasoconstriction and aldosterone secretion. However, ARBs are affected by drug metabolism enzyme gene polymorphism, which leads to individual differences in their antihypertensive efficacy [15]. There are few literature reports on whether the antihypertensive effect of ARBs is affected by intestinal flora.…”

Section: Introductionmentioning

confidence: 99%

Lactobacillus induced by irbesartan on spontaneously hypertensive rat contribute to its antihypertensive effect

Xiong,

He,

Chen

et al. 2023

Journal of Hypertension

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Objective: Hypertension is linked to gut dysbiosis. Here, the impact of the angiotensin receptor antagonist irbesartan on the gut microbiota of spontaneously hypertensive rats (SHR) were investigated. In addition, we assessed their contribution to its antihypertensive effect. Methods: Eight-week-old Wistar–Kyoto (WKY) rats and SHR were administered irbesartan for 8 weeks. Fecal microbiota transplantation (FMT) was performed from SHR treated with irbesartan or untreated SHR to recipient untreated SHR. The preventive effect of Lactobacillus on hypertension in SHR was evaluated. Blood pressure (BP) was calculated using a tail-sleeve sphygmomanometer. To better assess the composition of the gut microbiota, the V3–V4 region of the 16S rRNA gene was amplified while short-chain fatty acids (SCFAs) in feces were tested by liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS). Results: Irbesartan restored gut dysbiosis, increased the abundance of Lactobacillus, and improved anti-inflammatory ability, antioxidative ability, intestinal integrity, and intestinal inflammation in SHR. The microbiota in SHR-treated irbesartan could reduce BP and improve antioxidative ability and gut integrity in SHR. Lactobacillus johnsonii (L. johnsonii) and Lactobacillus reuteri (L. reuteri) reduced BP, restored gut dysbiosis and improved anti-inflammatory ability, antioxidative ability, intestinal integrity in SHR. Most notably, irbesartan, L. johnsonii, and L. reuteri can significantly increase SCFA content in SHR feces. Conclusion: The current study demonstrated that irbesartan treatment ameliorated gut dysbiosis in SHR. Irbesartan induced alterations in gut microbiota, with increased prevalence of Lactobacillus.

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Influence of CYP2C9 Genetic Polymorphisms on the Pharmacokinetics of Losartan and Its Active Metabolite E-3174: A Systematic Review and Meta-Analysis

Cited by 13 publications

References 32 publications

Personalized antihypertensive treatment guided by pharmacogenomics in China

Personalized antihypertensive treatment guided by pharmacogenomics in China

In Silico Analysis of 14-Deoxy 11, 12-Didehydro Andrographolide (AGP 2) from Sambiloto (Andrographis paniculata) as Drug Candidate Against SARS-CoV-2

Lactobacillus induced by irbesartan on spontaneously hypertensive rat contribute to its antihypertensive effect

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