Prasugrel Research Articles

The Degradation Chemistry of Prasugrel Hydrochloride: Part 1—Drug Substance

Prasugrel hydrochloride is the active ingredient in Effient™, a thienopyridine platelet inhibitor. An extensive study of the degradation chemistry of prasugrel hydrochloride (LY640315 hydrochloride) has been carried out on the drug substance (part I) and on the drug product (part II, future article) using a multidimensional approach including hydrolytic, oxidative, and photolytic stressing, computational chemistry, HPLC analysis, and structure elucidation by various spectroscopic techniques. The major degradation products formed from the drug substance under the various stress conditions have been isolated and structures unambiguously determined, and the pathways leading to these products have been proposed. Fourteen new (not previously disclosed) products were discovered and characterized, in addition to 4 degradation products that had been previously identified in the literature. The pathways indicate that prasugrel is susceptible to hydrolysis, autoxidation (both radical-initiated and single-electron mediated), and peroxide-mediated oxidation; in solution, prasugrel is susceptible to photodegradation.

Dissolution Rate Improvement of Prasugrel Hydrochloride by Solid Dispersion Method Using HPMC-AS as a Polymer

Dissolution Rate Improvement of Prasugrel Hydrochloride by Solid Dispersion Method Using HPMC-AS as a Polymer

Electrochemical simulation of three novel cardiovascular drugs phase I metabolism and development of a new method for determination of them by liquid chromatography coupled with tandem mass spectrometry

In this study electrochemistry (EC) coupled with electrospray ionization mass spectrometry (ESI-MS) was used to study the metabolic fate of three novel cardiovascular drugs: rivaroxaban (RIV), aliskiren (ALS), and prasugrel (PRS). Mimicry of the oxidative phase I metabolism was achieved in a simple amperometric thin-layer cell equipped with a boron-doped diamond (MD) working electrode. Structures of the electrochemically-generated metabolites were elucidated from MS/MS experiments. Additionally, a sensitive, specific, and rapid ultra-high performance liquid chromatography–tandem mass spectrometer (UHPLC–MS/MS) method has been developed and validated for the selected drugs in human urine samples. Three different sample preparation methods were compared and finally, sample preparation was accomplished through an ultrasound-assisted emulsification microextraction process (USAEME). The drugs were detected using a triple quadrupole tandem mass spectrometer by multiple reaction monitoring via an electrospray ionization source with positive ionization mode (ESI(+)). The results obtained by EC–MS were compared with conventional in vivo studies by analyzing urine samples from patients. Data from in vivo experiments showed good agreement with the data from electrochemical oxidation. Thus, EC–MS is very well-suited for the simulation of the oxidative metabolism of rivaroxaban, aliskiren, and prasugrel as well. Moreover, electrochemical conversion of target compounds appears to be a new in vitro technology for the prediction of potential metabolites.

Adherence to Platelet Inhibitor Therapy Following Percutaneous Coronary Intervention

The antiplatelet drugs clopidogrel, prasugrel, and ticagrelor (Brilinta) are prescribed following percutaneous coronary intervention (PCI). In this

Trends in Platelet Adenosine Diphosphate P2Y12 Receptor Inhibitor Use and Adherence Among Antiplatelet-Naive Patients After Percutaneous Coronary Intervention, 2008-2016

Current guidelines recommend prasugrel hydrochloride and ticagrelor hydrochloride as preferred therapies for patients with acute coronary syndrome (ACS) treated with percutaneous coronary intervention (PCI). However, it is not well known how frequently these newer agents are being used in clinical practice or how adherence varies among the platelet adenosine diphosphate P2Y12 receptor (P2Y12) inhibitors. To determine trends in use of the different P2Y12 inhibitors in patients who underwent PCI from 2008 to 2016 in a large cohort of commercially insured patients and differences in patient adherence and costs among the P2Y12 inhibitors. A retrospective cohort study used administrative claims from a large US national insurer (ie, UnitedHealthcare) from January 1, 2008, to December 1, 2016, comprising patients aged 18 to 64 years hospitalized for PCI who had not received a P2Y12 inhibitor for 90 days preceding PCI. The P2Y12 inhibitor filled within 30 days of discharge was identified from pharmacy claims. Proportion of patients filling prescriptions for P2Y12 inhibitors within 30 days of discharge by year, as well as medication possession ratios (MPRs) and total P2Y12 inhibitor copayments at 6 and 12 months for patients who received drug-eluting stents. A total of 55 340 patients (12 754 [23.0%] women; mean [SD] age, 54.4 [7.1] years) who underwent PCI were included in this study. In 2008, 7667 (93.6%) patients filled a prescription for clopidogrel bisulfate and 521 (6.4%) filled no P2Y12 inhibitor prescription within 30 days of hospitalization. In 2016, 2406 (44.0%) patients filled clopidogrel prescriptions, 2015 (36.9%) filled either prasugrel or ticagrelor prescriptions, and 1045 (19.1%) patients filled no P2Y12 inhibitor prescription within 30 days of hospitalization. At 6 months, mean MPRs for patients who received a drug-eluting stent filling clopidogrel, prasugrel, and ticagrelor prescriptions were 0.85 (interquartile range [IQR], 0.82-1.00), 0.79 (IQR, 0.66-1.00), and 0.76 (IQR, 0.66-0.98) (P < .001), respectively; mean copayments for a 6 months' supply were $132 (IQR, $47-$203), $287 (IQR, $152-$389), and $265 (IQR, $53-$387) (P < .001), respectively. At 12 months, mean MPRs for clopidogrel, prasugrel, and ticagrelor were 0.76 (IQR, 0.58-0.99), 0.71 (IQR, 0.49-0.98), and 0.68 (IQR, 0.41-0.94) (P < .001), respectively; mean total copayments were $251 (IQR, $100-$371), $556 (IQR, $348-$730), and $557 (IQR, $233-$744) (P < .001), respectively. Between 2008 and 2016, increased use of prasugrel and ticagrelor was accompanied by increased nonfilling of prescriptions for P2Y12 inhibitors within 30 days of discharge. Prasugrel and ticagrelor had higher patient costs and lower adherence in the year following PCI compared with clopidogrel. The introduction of newer, more expensive P2Y12 inhibitors was associated with lower adherence to these therapies.

Platelet reactivity in patients with acute coronary syndrome treated with prasugrel or ticagrelor in comparison to clopidogrel: a retrospective pharmacodynamic analysis

Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 inhibitor is a mainstay of the prevention of stent thrombosis following percutaneous coronary intervention (PCI). In the 2015 European guidelines for the management of acute coronary syndrome (ACS), prasugrel (PRA) and ticagrelor (TICA) combined with aspirin are recommended as first-line therapy. Clopidogrel (CLO) is recommended as an alternative medication for patients with contradictions to these new drugs.This single-center study analyzed the platelet function of 809 ACS patients undergoing PCI and treatment with DAPT. The platelet response to ADP was determined using Multiplate® analyzer at a median of 3 days after PCI in 254 patients treated with PRA (loading dose [LD] 60 mg, 10 mg qd), 162 patients receiving TICA (LD 180 mg, D 90 mg bid), and 393 CLO-treated patients (LD 600 mg, 75 mg qd). An aggregation >468 arbitrary units (AU)*min was defined as “high on-treatment platelet reactivity” (HPR), <188 AU*min as “low on-treatment platelet reactivity” (LPR).Platelet response in PRA-treated patients was lower compared to CLO or TICA (median; interquartile range: PRA 220 [163–275] AU*min vs. CLO 268 [186–387] AU*min, p < 0.001 vs. TICA 245 [190–320] AU*min, p = 0.001). Only 1.6% of PRA patients were stratified as HPR and 34.6% as LPR, while in the TICA group 1.9% fulfilled the criteria of HPR and 24.1% criteria of LPR. Sixteen percent of CLO patients were stratified as HPR and 26.2% as LPR.In a real-world cohort of ACS patients following PCI, PRA results in more potent inhibition of platelet function compared to CLO and TICA. TICA achieves a consistent antiplatelet effect with reduced rates of HPR and LPR in relation to CLO.

Identification and characterization of the degradation products of prasugrel hydrochloride tablets using LC-MS technique

ABSTRACTNew high-performance liquid chromatography method was developed for the determination of prasugrel HCl-related substances. Impurity profile of prasugrel HCl was established by studying the degradation profile of it as an active pharmaceutical ingredient, for the first time, in the tablet form. Two significant unknown degradation products (impurities) were detected and characterized, to the best of our knowledge; these impurities have not been previously reported in the literature. The first one resulted from acidic, basic, and neutral hydrolyses of prasugrel; it was nominated as impurity 1 (5-(2-cyclopropyl-1-(2-fluorophenyl)-2-oxoethyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2(3H)-one), its structure was proposed using liquid chromatography/mass spectrometry technique. The second degradant was nominated as impurity 2 (5-(2-cyclopropyl-1-(2-fluorophenyl)-2-oxoethyl)-7a-hydroxy-5,6,7,7a-tetrahydrothieno[3,2-c]pyridin-2(4H)-one) that formed upon neutral hydrolysis of prasugrel with magnesium stearate; this impurity was identified using nuclear magnetic resonance and LC-MS techniques. Based on these findings, other lubricant materials should be used in prasugrel tablets instead of magnesium stearate to avoid formation of such impurity. Prasugrel HCl was susceptible to hydrolytic and oxidative degradation, whereas it was stable under these conditions.

Determination of Prasugrel Hydrochloride in Bulk and Pharmaceutical Formulation Using New Ion Selective Electrodes

The construction and performance characteristics of Prasugrel hydrochloride (PRS) selective electrodes were developed. Electrodes were based on the incorporation of PRS with pairing agents, Ammonium Molybdate (MOL) and Nessler reagent (NES). The electrodes displayed a Nernstian response with a mean calibration graphs slopes of 59.21, 27.57 mv.decade-1 for the two electrodes respectively, over linear concentration range 10-2 –10-5 mol L-1 of the drug, with detection limits 0.063, 0.090 µM and quantification limits 0.27, 0.192 µM for electrode 1 and 2 respectively. The safe pH range of the proposed electrodes was (1-4). The influence of possible interfering species such as inorganic cations and pharmacologically related compounds was studied. The electrodes showed a fast response of (20 ± 2 sec, 17 ± 2 sec) for a period of 11 days, 9 days for electrode 1 and 2 respectively without significant change in electrode parameters. The methods are precise as shown by mean recoveries range of (97.7-102.5 %) – (97.3-101 %) with a mean relative standard deviation less than 3.14 and 4.46% for electrode 1 and 2 respectively. The results were compared to those obtained by a reference method. The proposed electrodes were used for the determination of PRS in pure form and pharmaceutical formulation.

Association of Novel Oral Antithrombotics With the Risk of Intraocular Bleeding

ImportanceNovel oral anticoagulation and antiplatelet therapies have become a mainstay of treatment for thromboembolic disease. However, the safety profile of these medications has not been completely characterized.ObjectiveTo determine the risk of developing intraocular hemorrhages with novel oral antithrombotic therapy compared with that of traditional antithrombotic agents.Design, Setting, and ParticipantsIn this retrospective cohort study, a large national insurance claims database was used to generate 2 parallel analyses. All patients with incident use of dabigatran etexilate or rivaroxaban between January 1, 2010, and September 30, 2015, were compared with patients with incident use of warfarin sodium. Similarly, patients with new use of prasugrel hydrochloride were compared with those with new use of clopidogrel bisulfate. Both analyses required the patient to be in the insurance plan for at least 24 months prior to initiation of therapy and excluded patients with any previous diagnosis of intraocular hemorrhages or any prescription for the comparator medications. Furthermore, the antiplatelet analysis required a diagnosis of acute coronary syndrome or a myocardial infarction within 60 days of initiation of pharmacologic therapy. The anticoagulant analysis excluded patients with end-stage renal disease, renal transplants, and those with heart valve disease.Main Outcomes and MeasuresIncident intraocular hemorrhages at 90 and 365 days. Multivariate Cox proportional hazards regression models were used to compare the hazard ratio (HR) of developing an intraocular hemorrhage in individuals taking novel agents compared with those taking traditional medications.ResultsA total of 146 137 patients taking warfarin (76 714 women and 69 423 men; mean [SD] age, 69.8 [11.8] years) were compared with 64 291 patients taking dabigatran or rivaroxaban (31 576 women and 32 715 men; mean [SD] age, 67.6 [11.7] years). Cox proportional hazards regression revealed a decreased hazard for developing an intraocular hemorrhage with dabigatran or rivaroxaban at 365 days (HR, 0.75; 95% CI, 0.58-0.97; P = .03), but not at 90 days (HR, 0.73; 95% CI, 0.22-2.63; P = .13). A total of 103 796 patients taking clopidogrel (37 578 women and 66 218 men; mean [SD] age, 68.0 [11.3] years) were compared with 8386 patients taking prasugrel (1988 women and 6380 men; mean [SD] age, 61.0 [9.6] years) and no increased hazard for developing an intraocular hemorrhage with prasugrel was seen at 90 days (HR, 0.75; 95% CI, 0.29-1.92; P = .55) or 365 days (HR, 1.19; 95% CI, 0.69-2.04; P = .53).Conclusions and RelevanceThese results suggest a decreased risk of intraocular hemorrhage associated with novel direct thrombin inhibitors and direct factor Xa inhibitors, but no difference for P2Y12 inhibitors compared with traditional vitamin K anticoagulation and antiplatelet therapy, respectively.

Prasugrel vs. Ticagrelor in Acute Myocardial Infarction Treated with Primary Angioplasty

Prasugrel and ticagrelor are class Ia antiplatelet medications recommended for ST-segment elevation myocardial infarction (STEMI) patients treated with

Clinical trial conduct in special populations and developing regions: An overview of the DOVE study in pediatric patients with sickle cell disease

Clinical trials conducted in unique patient populations or individuals with rare diseases are typically hampered by limitations in availability of qualified patients, requiring sponsors to broaden their global outreach to achieve enrollment. Engaging clinical study centers in developing regions may offer access to a substantially larger patient pool. However, they provide a unique set of challenges based on local cultures and requirements. The DOVE study (Determining effects Of platelet inhibition on Vaso-occlusive Events) was a clinical trial of prasugrel hydrochloride (prasugrel) in pediatric patients (aged 2 to <18years) with sickle cell anemia. The study was conducted at centers located in both well-developed and developing regions, enrolling 341 children. Study planning and execution required careful consideration of cultural requirements in each region and implementation of additional trial initiation and execution processes to address those needs. Innovative strategies were employed to ensure global consistency and quality in study execution. Significant regional- and country-specific differences were observed in site activation and enrollment. Although site activation processes were more complex and slower in developing countries, enrollment rates were much higher, which helped mitigate the site activation delays and allowed significant contribution to complete study enrollment. Data quality and patient retention in developing countries were equivalent to those observed in more developed countries, further supporting the ability to successfully conduct high-quality global registration trials in those countries. This report provides an overview of the experiences in site identification, site qualification, enrollment, patient retention, and data quality assurance in the DOVE study.

De-Escalating Antiplatelet Therapy: A Promising Concept

Prasugrel has shown superiority over clopidogrel with regard to cardiovascular outcomes in patients with an acute coronary syndrome and percutaneous

Prasugrel hydrochloride for the treatment of sickle cell disease

ABSTRACTIntroduction: Therapeutic options for sickle cell disease (SCD) are limited and, currently, only one drug (hydroxyurea) has FDA approval for the treatment of adult SCD. While this genetic disease is caused by hemoglobin polymerization, subsequent downstream events trigger platelet activation, vaso-occlusion and the disease’s complex pathophysiology.Areas covered: The oral thienopyridine, prasugrel hydrochloride, irreversibly inhibits the P2Y12 receptors, inhibiting ADP-dependent platelet activation. We discuss recent clinical trials evaluating the pharmokinetics of prasugrel and its potential for use in SCD.Expert opinion: Prasugrel administration in SCD appears to be well tolerated and safe. However, although this drug modestly inhibits platelet activity in these patients, administration of prasugrel to a large group of children and adolescents for up to 24 months failed to convincingly reduce vaso-occlusive complications. Speculatively, prasugrel may be of occasional use for off-license purposes in patients unable or unwilling to take hydroxyurea (particularly in 12–17-year olds). Although there is currently no prospect of prasugrel being licensed for use in SCD, the success of on-going trials of other antiplatelet agents in SCD might lead to further trials of prasugrel in SCD.

Dual Antithrombotic vs. Dual Antiplatelet Strategy After Acute Coronary Syndrome

Although dual antiplatelet therapy (DAPT) with a P2Y12 inhibitor (clopidogrel, prasugrel, or ticagrelor) and aspirin is the standard of care after an acute coronary syndrome (ACS), major cardiovascular events still occur after ACS in almost 10% of patients. Adding low-dose rivaroxaban, an anticoagulant, to DAPT resulted in a decrease in ischemic outcomes but increased major bleeding events (NEJM JW Cardiol Jan 2012 and N Engl …

Prasugrel suppresses development of lithium-induced nephrogenic diabetes insipidus in mice.

Previously, we localized ADP-activated P2Y12 receptor (R) in rodent kidney and showed that its blockade by clopidogrel bisulfate (CLPD) attenuates lithium (Li)-induced nephrogenic diabetes insipidus (NDI). Here, we evaluated the effect of prasugrel (PRSG) administration on Li-induced NDI in mice. Both CLPD and PRSG belong to the thienopyridine class of ADP receptor antagonists. Groups of age-matched adult male B6D2 mice (N=5/group) were fed either regular rodent chow (CNT), or with added LiCl (40mmol/kg chow) or PRSG in drinking water (10mg/kg bw/day) or a combination of LiCl and PRSG for 14days and then euthanized. Water intake and urine output were determined and blood and kidney tissues were collected and analyzed. PRSG administration completely suppressed Li-induced polydipsia and polyuria and significantly prevented Li-induced decreases in AQP2 protein abundance in renal cortex and medulla. However, PRSG either alone or in combination with Li did not have a significant effect on the protein abundances of NKCC2 or NCC in the cortex and/or medulla. Immunofluorescence microscopy revealed that PRSG administration prevented Li-induced alterations in cellular disposition of AQP2 protein in medullary collecting ducts. Serum Li, Na, and osmolality were not affected by the administration of PRSG. Similar to CLPD, PRSG administration had no effect on Li-induced increase in urinary Na excretion. However, unlike CLPD, PRSG did not augment Li-induced increase in urinary arginine vasopressin (AVP) excretion. Taken together, these data suggest that the pharmacological inhibition of P2Y12-R by the thienopyridine group of drugs may potentially offer therapeutic benefits in Li-induced NDI.

Identification and Characterization of Prasugrel Degradation Products by GC/MS, FTIR and 1H NMR

The objective of the present work was to separate, identify and characterize the degradation products of Prasugrel hydrochloride under hydrolytic and oxidative stress conditions according to the International Conference on Harmonization (ICH) guideline Q1A (R2). The drug degraded under acidic, basic, and oxidative stress. Five degradation products were formed, which were separated using preparative TLC. Mass fragmentation pathway of the drug was first established with the help of GC/MS studies. The degradation products were subjected to FTIR and 1H NMR studies. The obtained mass spectral data were employed to characterize the degradation products and assign structures. The degradation products were identified as 5-(2cyclopropyl-1-(2-fluorophenyl)-2-oxoethyl)-4, 5, 6, 7-tetrahydrothieno[3, 2-c]pyridin-2(3H)-one, 5-(2-cyclopropyl1-(2-fluorophenyl)-2-oxoethyl)-5, 6, 7, 7a-tetrahydrothieno[3, 2-c]pyridin-2(4H)-one, 2-acetoxy-5-(2-cyclopropyl1-(2-fluorophenyl)-2-oxoethyl)-4, 5, 6, 7-tetrahydrothieno[3, 2-c]pyridine 5-oxide, 1-cyclopropyl-2-(2fluorophenyl)ethane-1, 2-dione and 4, 5, 6, 7-tetrahydrothieno[3, 2-c]pyridin-2-yl acetate.

CLOPIDOGREL VERSUS PRASUGREL IN PATIENTS UNDERGOING ELECTIVE PERCUTANEOUS CORONARY INTERVENTION

Objective: To compare short term clinical outcomes in patients on Clopidogreland Prasugrel undergoing elective percutaneous coronary interventions. Methodology: This comparative study was conducted in Department ofCardiology department, Postgraduate Medical Institute Govt. Lady ReadingHospital Peshawar from 1st June 2012 to 31st March 2013. Patients undergoingelective PCI for significant lesions on coronary angiography of both gendershaving weight 60 Kg and baseline platelets aggregation5 ohm. All patients were followed for 1 month. Results: A total of 148 patients were included in the study. Group A had 74patients using Clopidogrel and group B contained 74 patients using Prasugrel.Group A had 55 (74.3%) males while group B had 56 (75.7%) males (p=0.85).Mean age was 54.9±11.2 years in group A and 57.7±8.7 years in group B (p=0.09). Mean percent difference between basal and follow up platelet aggregationwas 52.96±24.77 ohm in group A and 82.25±14.34 ohm in group B (p=0.001). At 01 month follow up 03 (4%) episodes of major bleeding occurred inPrasugrel group which led to discontinuation of the drug while minor bleedingepisodes in 7 (9.5%) patients. There was NSTEMI ACS in 3 (4.1%) patients andSTEMI in 01 (1.35%) in Clopidogrel group while 2 STEMI patients in Prasugrelgroup. Number of deaths were 2 in prasugrel group and 1 in clopidogrel groupComposite of death, major bleeding, stroke, ACS was 7 (9.5%) in Prasugrelgroup and 6 (8%) in Clopidogrel group (p=0.09). Conclusion: There is no short term clinical benefit of Prasugrel over Clopidogrelin elective percutaneous coronary intervention. Key Words: Bleeding, Clopidogrel, Prasugrel, Percutaneous CoronaryIntervention

Prasugrel hydrochloride for the treatment of acute coronary syndrome patients

ABSTRACTIntroduction: Dual antiplatelet therapy (DAPT) with aspirin combined with either a thienopyridine (clopidogrel or prasugrel) or acyclopentyl-triazolo-pyrimidine (ticagrelor) plays a vital role in the management of acute coronary syndrome (ACS) especially in those undergoing percutaneous coronary intervention (PCI) but even those being managed medically. Observational studies and some formal studies have shown patients on the standard dual antiplatelet regimen (clopidogrel and aspirin) continue to have further ischemic events and can suffer stent thrombosis. It has been demonstrated that clopidogrel is associated with a delayed onset of action with a considerable inter-individual variation to treatment thus making it difficult to achieve an optimal level of platelet inhibition.Areas covered: This article will review the current evidence that is available regarding the effectiveness and safety of prasugrel in ACS patients undergoing percutaneous coronary intervention (PCI).Expert commentary: Prasugrel is an oral third-generation inhibitor of platelet activation and aggregation. Laboratory studies and early phase clinical trials show prasugrel has a faster onset of action, is more potent and has reduced inter-patient response variability compared to clopidogrel. The published studies so far demonstrated that prasugrel when compared to clopidogrel also shows a higher degree of effectiveness in the prevention of platelet-initiated thrombotic events in patients with ACS undergoing PCI, however these benefits are offset somewhat by an increased bleeding risk.

Australian 6 Year Trends of Prescribing Rates and Costs of Clopidogrel, Prasugrel and Ticagrelor

Australian 6 Year Trends of Prescribing Rates and Costs of Clopidogrel, Prasugrel and Ticagrelor

Abstract WP278: Effects of Prasugrel on Cerebral Infarction and Neurological Deficits in a Non-human Primate Model of Thrombotic Stroke

Introduction: Several clinical trials have demonstrated the benefits of thienopyridine monotherapy in ischemic stroke patients. Non-human primate models of ischemic stroke have been used for various antithrombotic agents; however, to our knowledge, there is no data on the effects of P2Y 12 antagonists in a primate thrombotic middle cerebral artery occlusion (MCAO) model. Accordingly, it remains unclear what level of inhibition of platelet aggregation (IPA) by thienopyridine antiplatelet drugs is required for optimal treatment of ischemic stroke. Hypothesis: We assessed the hypothesis that prasugrel, the third-generation thienopyridine antiplatelet drug, would be effective in a non-human primate model of thrombotic stroke. Methods: Prasugrel hydrochloride was administered orally once daily for 3 d to cynomolgus monkeys. Ex vivo platelet aggregation induced by 5 μM ADP in platelet-rich plasma was determined before the 1st dose and 4, 5, 8 and 24 h after the final dose (N=4 per group). Thrombotic MCAO was induced photochemically by employing rose bengal 4 h after the final dose (N=8 per group). Cerebral infarct volume and neurological deficit score were determined 24 h after the MCAO. Results: Prasugrel showed significant and stable antiplatelet effects. The IPA on Day 3 ranged from 31.4% ± 8.0% to 36.4% ± 5.5% at 0.3 mg/kg/d and from 43.8% ± 6.6% to 49.8% ± 5.6% at 1 mg/kg/d. In the thrombotic MCAO model, prasugrel increased MCA patency in a dose-dependent manner. Prasugrel significantly reduced ischemic infarction to 755.1 ± 293.3 mm 3 ( P &lt;0.01) at 0.3 mg/kg/d and 333.2 ± 187.7 mm 3 ( P &lt;0.01) at 1 mg/kg/d compared to control (2641.8 ± 480.5 mm 3 ) without increasing hemorrhagic infarction. Prasugrel also significantly reduced neurological deficit scores to 14 ± 4 ( P &lt;0.05) at 0.3 mg/kg/d and 6 ± 3 ( P &lt;0.01) at 1 mg/kg/d compared to control (33 ± 3). Conclusions: Prasugrel is effective in the primate model of thrombotic stroke. These data suggest that prasugrel monotherapy would be beneficial in thrombotic stroke patients. In addition, this non-human primate model of photochemically induced MCA thrombosis is a useful model for stroke research.