Role of Lactone and Acid Forms in the Pleiotropic Effects of Statins

Preta, Giulio

doi:10.3390/pharmaceutics14091899

Cited by 4 publications

(1 citation statement)

References 12 publications

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“…The use of chitosan, PVA, and surfactant Tween 80 in the nanoformulation is responsible for the increased dissolution of simvastatin and influx against P-gp activity. The previous in vitro studies showed that the lactone ring in formulation F40 showed maximum stability in gastric pH, and no degradation of the lactone in 24 h was observed [ 25 , 26 ].…”

Section: Discussionmentioning

confidence: 99%

A Study on Pharmacokinetic Functionalities and Safety Margins of an Optimized Simvastatin Nanoformulation

et al. 2023

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A pharmaceutical formulation with favorable pharmacokinetic parameters is more likely to be efficacious and safe to overcome the failures of the drug resulting from lack of efficacy, poor bioavailability, and toxicity. In this view, we aimed to evaluate the pharmacokinetic functionalities and safety margin of an optimized CS-SS nanoformulation (F40) by in vitro/in vivo methods. The everted sac technique was used to evaluate the improved absorption of a simvastatin formulation. In vitro protein binding in bovine serum and mice plasma was performed. The formulation’s liver and intestinal CYP3A4 activity and metabolic pathways were investigated by the qRT-PCR technique. The excretion of cholesterol and bile acids was measured to demonstrate the formulation’s cholesterol depletion effect. Safety margins were determined by histopathology as well as fiber typing studies. In vitro protein binding results revealed the existence of a high percentage of free drugs (22.31 ± 3.1%, 18.20 ± 1.9%, and 16.9 ± 2.2%, respectively) compared to the standard formulation. The controlled metabolism in the liver was demonstrated from CYP3A4 activity. The formulation showed enhanced PK parameters in rabbits such as a lower Cmax, clearance, and a higher Tmax, AUC, Vd, and t1/2. qRT-PCR screening further proved the different metabolic pathways followed by simvastatin (SREBP-2) and chitosan (PPAR-γ pathway) in the formulation. The results from qRT-PCR and histopathology confirmed the toxicity level. Hence, this pharmacokinetic profile of the nanoformulation proved it has a unique synergistic hypolipidemic modality.

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Section: Discussionmentioning

confidence: 99%

A Study on Pharmacokinetic Functionalities and Safety Margins of an Optimized Simvastatin Nanoformulation

et al. 2023

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Advances in statin adverse reactions and the potential mechanisms: A systematic review

Zeng,

Deng,

Luo

et al. 2024

Journal of Advanced Research

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Microbial metabolism marvels: a comprehensive review of microbial drug transformation capabilities

Martinelli,

Thiele

2024

Gut Microbes

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This comprehensive review elucidates the pivotal role of microbes in drug metabolism, synthesizing insights from an exhaustive analysis of over two hundred papers. Employing a structural classification system grounded in drug atom involvement, the review categorizes the microbiome-mediated drug-metabolizing capabilities of over 80 drugs. Additionally, it compiles pharmacodynamic and enzymatic details related to these reactions, striving to include information on encoding genes and specific involved microorganisms. Bridging biochemistry, pharmacology, genetics, and microbiology, this review not only serves to consolidate diverse research fields but also highlights the potential impact of microbial drug metabolism on future drug design and in silico studies. With a visionary outlook, it also lays the groundwork for personalized medicine interventions, emphasizing the importance of interdisciplinary collaboration for advancing drug development and enhancing therapeutic strategies.

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Role of Lactone and Acid Forms in the Pleiotropic Effects of Statins

Abstract: Statins are a class of drugs used worldwide to lower low-density lipoprotein cholesterol [...]

Cited by 4 publications

References 12 publications

A Study on Pharmacokinetic Functionalities and Safety Margins of an Optimized Simvastatin Nanoformulation

A Study on Pharmacokinetic Functionalities and Safety Margins of an Optimized Simvastatin Nanoformulation

Advances in statin adverse reactions and the potential mechanisms: A systematic review

Microbial metabolism marvels: a comprehensive review of microbial drug transformation capabilities

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