<b>The discovery and development of prasugrel</b>

Shan, Jiaqi; Sun, Hongbin

doi:10.1517/17460441.2013.793668

Cited by 7 publications

(12 citation statements)

References 69 publications

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“…Prasugrel, a prodrug, (5-[2-cyclopropyl-1-(2-fluorophenyl)-2-oxoethyl]-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl acetate) is a novel and potent irreversible thienopyridine inhibitor of platelet aggregation [ 26 , 27 ]. Its conformational structure is, like in ticlopidine and clopidogrel, determined by dihedral angles α, β, δ, ε and ζ ( Table 1 , Figure 1 ).…”

Section: Resultsmentioning

confidence: 99%

A Comparative Study of Molecular Structure, pKa, Lipophilicity, Solubility, Absorption and Polar Surface Area of Some Antiplatelet Drugs

Remko

Remková

Broer

2016

IJMS

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Theoretical chemistry methods have been used to study the molecular properties of antiplatelet agents (ticlopidine, clopidogrel, prasugrel, elinogrel, ticagrelor and cangrelor) and several thiol-containing active metabolites. The geometries and energies of most stable conformers of these drugs have been computed at the Becke3LYP/6-311++G(d,p) level of density functional theory. Computed dissociation constants show that the active metabolites of prodrugs (ticlopidine, clopidogrel and prasugrel) and drugs elinogrel and cangrelor are completely ionized at pH 7.4. Both ticagrelor and its active metabolite are present at pH = 7.4 in neutral undissociated form. The thienopyridine prodrugs ticlopidine, clopidogrel and prasugrel are lipophilic and insoluble in water. Their lipophilicity is very high (about 2.5-3.5 logP values). The polar surface area, with regard to the structurally-heterogeneous character of these antiplatelet drugs, is from very large interval of values of 3-255 Å 2 . Thienopyridine prodrugs, like ticlopidine, clopidogrel and prasugrel, with the lowest polar surface area (PSA) values, exhibit the largest absorption. A high value of polar surface area (PSA) of cangrelor (255 Å 2 ) results in substantial worsening of the absorption in comparison with thienopyridine drugs.

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Section: Resultsmentioning

confidence: 99%

A Comparative Study of Molecular Structure, pKa, Lipophilicity, Solubility, Absorption and Polar Surface Area of Some Antiplatelet Drugs

Remko

Remková

Broer

2016

IJMS

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“…In 1993, Japanese researchers claimed the patent for a series of hydrothienopyridine derivatives with antithrombotic activity. 78,79 Among these, prasugrel was shown to have a greater antithrombotic effect than clopidogrel. Studies in rodents showed that it had additional properties, such as a longer and more intense effect.…”

Section: Clopidogrel Resistance In Interventional Neuroradiologymentioning

confidence: 99%

“…Studies in rodents showed that it had additional properties, such as a longer and more intense effect. 78 In 2009, the FDA approved prasugrel for use in patients with acute coronary syndrome undergoing percutaneous coronary intervention. 80 Prasugrel is also a prodrug and must be metabolized to be active.…”

Section: Clopidogrel Resistance In Interventional Neuroradiologymentioning

confidence: 99%

“…After being absorbed, it is rapidly esterase-hydrolyzed to an inactive thiolactone, which, in turn, is oxidized in the liver by CYP, leading to the formation of the active metabolite R-138727. 47,78 Despite being extensive, the metabolism of prasugrel is rapid. The presence of the active metabolite in the plasma approximately 15 minutes after its administration is a consequence of this phenomenon.…”

Section: Clopidogrel Resistance In Interventional Neuroradiologymentioning

confidence: 99%

“…81 Its half-life is around 7.4 hours, the maximum plasma concentration occurs around 30 minutes, and the antiplatelet action lasts for about 96 hours. 66,78,81 It is possible to obtain clinically meaningful levels of the active metabolite with daily maintenance doses of 5 or 10 mg, much lower than those used for clopidogrel (75 mg per day). 78 The activation, which occurs in 1 hepatic step, is different from that of clopidogrel, which requires a second oxidation stage.…”

Section: Clopidogrel Resistance In Interventional Neuroradiologymentioning

confidence: 99%

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Safety of Oral P2Y12 Inhibitors in Interventional Neuroradiology: Current Status and Perspectives

Camargo

Lima²,

Janot

et al. 2021

AJNR Am J Neuroradiol

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In the field of interventional neuroradiology, antiplatelet agents are commonly used to prepare patients before the implantation of permanent endovascular materials. Among the available drugs, clopidogrel is the most frequently used one, but resistance phenomena are considered to be relatively common. Prasugrel and ticagrelor were recently added to the pharmacologic arsenal, but the safety of these agents in patients undergoing neurointerventional procedures is still a subject of discussion. The cumulative experience with both drugs is less extensive than that with clopidogrel, and the experience with patients in the neurology field is less extensive than in the cardiology domain. In the present article, we provide a narrative review of studies that investigated safety issues of oral P2Y12 inhibitors in interventional neuroradiology and discuss potential routes for future research.

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Prasugrel Use Following PCI and Associated Patient Outcomes: Insights From the National VA CART Program

Aggarwal

Armstrong

Liu

et al. 2016

Clinical Cardiology

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BACKGROUND Although non-vitamin K antagonist oral anticoagulants (NOACs) do not require frequent laboratory monitoring, each compound requires dose adjustments on the basis of certain clinical criteria. OBJECTIVES This study assessed the frequency of off-label NOAC doses among AF patients and the associations between off-label dose therapy and clinical outcomes in community practice. METHODS We evaluated 5,738 patients treated with a NOAC at 242 ORBIT-AF II (Outcomes Registry for Better Informed Treatment of Atrial Fibrillation phase II) sites. NOAC doses were classified as either underdosed or overdosed, consistent with Food and Drug Administration labeling. Longitudinal outcomes (median follow-up: 0.99 years) included stroke or systemic embolism, myocardial infarction, major bleeding (International Society of Thrombosis and Haemostasis criteria), cause-specific hospitalization, and all-cause mortality. RESULTS Overall, 541 NOAC-treated patients (9.4%) were underdosed, 197 were overdosed (3.4%), and 5,000 were dosed according to U.S. labeling (87%). Compared with patients receiving the recommended dose, those who were receiving off-label doses were older (median: 79 and 80 years of age vs. 70 years of age, respectively; p < 0.0001), more likely female (48% and 67% vs. 40%, respectively; p < 0.0001), less likely to be treated by an electrophysiologist (18% and 19% vs. 27%, respectively; p < 0.0001), and had higher CHA2DS2-VASc scores (96% and 97% ≥2 vs. 86%, respectively; p < 0.0001) and higher ORBIT bleeding scores (25% and 31% >4 vs. 11%, respectively; p < 0.0001). After dose adjustment, NOAC overdosing was associated with increased all-cause mortality compared with recommended doses (adjusted hazard ratio: 1.91; 95% confidence interval [CI]: 1.02 to 3.60; p = 0.04). Underdosing was associated with increased cardiovascular hospitalization (adjusted hazard ratio: 1.26; 95% CI: 1.07 to 1.50; p = 0.007). CONCLUSIONS A significant minority (almost 1 in 8) of U.S. patients in the community received NOAC doses inconsistent with labeling. NOAC over- and underdosing are associated with increased risk for adverse events.

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The discovery and development of prasugrel

Cited by 7 publications

References 69 publications

A Comparative Study of Molecular Structure, pKa, Lipophilicity, Solubility, Absorption and Polar Surface Area of Some Antiplatelet Drugs

A Comparative Study of Molecular Structure, pKa, Lipophilicity, Solubility, Absorption and Polar Surface Area of Some Antiplatelet Drugs

Safety of Oral P2Y12 Inhibitors in Interventional Neuroradiology: Current Status and Perspectives

Prasugrel Use Following PCI and Associated Patient Outcomes: Insights From the National VA CART Program

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