Toxicology of Chiral Drugs

Yang, Guang; Bu, Hai‐Zhi

doi:10.1002/9781118075647.ch10

Cited by 3 publications

(6 citation statements)

References 83 publications

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“…15 İzomer karışımları, bazı durumlarda ilaç güvenliliği sorunları ile ilişkili olabilir. 7,10 Advers ilaç reaksiyonu (AİR), Dünya Sağlık Örgütü tarafından, "Hastalık profilaksisi, teşhisi ve tedavisinde ya da fizyolojik fonksiyonu değiştirmek amacıyla normal dozda alınan ilaca karşı insanda gelişen zararlı ve amaçlanmayan cevap." şeklinde tanımlanmıştır.…”

Section: Temel Tanımlar Ve Kavramlarunclassified

“…5 Nitekim kiralite, ilaçların farmakokinetik ve farmakodinamik özelliklerini değiştirebileceği gibi ilaç etkileşimleriyle veya toksikolojik yanıtlarıyla çeşitli güvenlilik sorunlarına da zemin hazırlayabilir. 10,20,23,41 Bazı kiral bileşiklerde enantiyomerlerden biri istenen terapötik etkiyi oluştururken, diğeri bu terapötik etkiden yoksun olabildiği gibi çeşitli güvenlilik sorunlarına da yol açabilir. Örneğin D-penisilamin söz konusu nedenden ötürü saf izomer formunda piyasaya giren bir ilaçtır.…”

Section: Temel Tanımlar Ve Kavramlarunclassified

“…8 Ayna görüntüsü ile örtüşmeyen moleküllerin önemli bir özelliği olan kiralite, ilaç gibi biyoaktif moleküllerin tasarım ve geliştirme süreçlerindeki belirleyici rolü nedeniyle ilaç etkililiği ve güvenliliği açısından önemli bir unsur konumuna gelmiştir. 7,9,10 Bu derlemede, kiralitenin güvenlilik sorunları ile olası ilişkileri perspektifinde ilaçlarda kiralite kavramının ele alınması amaçlanmıştır.…”

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See 2 more Smart Citations

The Concept of Chirality and its Association with Drug Safety: Traditional Review

BAHAR¹,

SONMEZ²,

VIZDIKLAR³

et al. 2022

J Lit Pharm Sci

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Section: Temel Tanımlar Ve Kavramlarunclassified

unclassified

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The Concept of Chirality and its Association with Drug Safety: Traditional Review

BAHAR¹,

SONMEZ²,

VIZDIKLAR³

et al. 2022

J Lit Pharm Sci

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show abstract

“…In addition to variable pharmacodynamic properties, numerous studies have shown that the individual enantiomers of a chiral drug often display stereoselectivity in pharmacokinetics, toxicity, and drug disposition, particularly in the area of drug metabolism. Stereochemical aspects associated with the metabolism and toxicity of chiral drugs have been reported [140]. Enantiomers may result in stereoselective toxicity due to pharmacodynamic and pharmacokinetic differences between enantiomers.…”

Section: Toxicologymentioning

confidence: 99%

“…Pharmacology and toxicological effects can coexist in the same enantiomer or both. In this context, clinical superiority of escitalopram, Ralbuterol and cyclophosphamide still need to be demonstrated [140]. The R-(-) fenoprofen enantiomer is metabolically inverted to the S-(+) fenoprofen enantiomer in the liver and severe hepatic disease should alter the percentage of chiral inversion obtained for R-(-) fenoprofen.…”

Section: Toxicologymentioning

confidence: 99%

Exploiting the Power of Stereochemistry in Drugs: An Overview of Racemic and Enantiopure Drugs

Sekhon¹

2013

J. Mod. Med. Chem.

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Stereochemistry is one of the essential dimensions in pharmacology as it dictates how enantiomers interact with biological systems. Chirality is very important in drug design. Enantiomers of the same chiral drug can have different pharmacodynamic and/or pharmacokinetic properties. In this context, replacing some existing racemates with single isomers has resulted in improved safety and/or efficacy profile of various racemates. Single enantiomer drug use can potentially lead to simpler and more selective pharmacologic profiles, improved therapeutic indices, simpler pharmacokinetics due to different rates of metabolism of the different enantiomers, decreased drug interactions, and drug companies are increasingly using chiral switching as a marketing strategy. Additionally, due to different pharmacological activity, enantiomers of chiral drugs can differ in toxicity. However, unpredicted toxicity has been reported in some chiral switching cases which has resulted the withdrawal of the enantiomer from the market or a halt in its development. In view of above, before switching to single enantiomer drugs, prescribers should look for evidence from well-conducted clinical trials to prove that the chiral switch is cost-effective and improves the outcomes for patients rather than patents. The U.S. Food and Drug Administration (FDA) have allowed single enantiomers of generic drugs to be patented and marketed under different name. FDA regulations require that all chiral bioactive drug molecules must be isolated and tested for the efficacy and safety, and have to be as pure as possible containing a single pure enantiomer.

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Interconversion-controlled liquid–liquid phase separation in a molecular chiral model

Uralcan

Longo

Анисимов

et al. 2021

The Journal of Chemical Physics

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Liquid–liquid phase separation of fluids exhibiting interconversion between alternative states has been proposed as an underlying mechanism for fluid polyamorphism and may be of relevance to the protein function and intracellular organization. However, molecular-level insight into the interplay between competing forces that can drive or restrict phase separation in interconverting fluids remains elusive. Here, we utilize an off-lattice model of enantiomers with tunable chiral interconversion and interaction properties to elucidate the physics underlying the stabilization and tunability of phase separation in fluids with interconverting states. We show that introducing an imbalance in the intermolecular forces between two enantiomers results in nonequilibrium, arrested phase separation into microdomains. We also find that in the equilibrium case, when all interaction forces are conservative, the growth of the phase domain is restricted only by the system size. In this case, we observe phase amplification, in which one of the two alternative phases grows at the expense of the other. These findings provide novel insights on how the interplay between dynamics and thermodynamics defines the equilibrium and steady-state morphologies of phase transitions in fluids with interconverting molecular or supramolecular states.

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Toxicology of Chiral Drugs

Cited by 3 publications

References 83 publications

The Concept of Chirality and its Association with Drug Safety: Traditional Review

The Concept of Chirality and its Association with Drug Safety: Traditional Review

Exploiting the Power of Stereochemistry in Drugs: An Overview of Racemic and Enantiopure Drugs

Interconversion-controlled liquid–liquid phase separation in a molecular chiral model

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