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Piechowski-Jozwiak B, Abidi E, El Nekidy WS, et al. Clinical Pharmacokinetics and Pharmacodynamics of Desmoteplase. Eur J Drug Metab Pharmacokinet. 2021;doi: 10.1007/s13318-021-00743-8.
Piechowski-Jozwiak, B., Abidi, E., El Nekidy, W. S., & Bogousslavsky, J. (2021). Clinical Pharmacokinetics and Pharmacodynamics of Desmoteplase. European journal of drug metabolism and pharmacokinetics, . https://doi.org/10.1007/s13318-021-00743-8
Piechowski-Jozwiak, Bartlomiej, et al. "Clinical Pharmacokinetics and Pharmacodynamics of Desmoteplase." European journal of drug metabolism and pharmacokinetics vol. (2021). doi: https://doi.org/10.1007/s13318-021-00743-8
Piechowski-Jozwiak B, Abidi E, El Nekidy WS, Bogousslavsky J. Clinical Pharmacokinetics and Pharmacodynamics of Desmoteplase. Eur J Drug Metab Pharmacokinet. 2021 Dec 11; doi: 10.1007/s13318-021-00743-8. Epub 2021 Dec 11. PMID: 34893967; PMCID: PMC8664670.
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Eur J Drug Metab Pharmacokinet. 2021 Dec 11; doi: 10.1007/s13318-021-00743-8. Epub 2021 Dec 11.

Clinical Pharmacokinetics and Pharmacodynamics of Desmoteplase.

European journal of drug metabolism and pharmacokinetics

Bartlomiej Piechowski-Jozwiak, Emna Abidi, Wasim S El Nekidy, Julien Bogousslavsky

Affiliations

  1. Neurological Institute, Cleveland Clinic Abu Dhabi, Abu Dhabi, UAE.
  2. Cleveland Clinic Lerner College of Medicine of Case Western University, Cleveland, OH, USA.
  3. Department of Neurology, King's College Hospital, Denmark Hill, London, SE5 9RS, UK.
  4. Department of Pharmacy, Cleveland Clinic Abu Dhabi, Abu Dhabi, UAE. [email protected].
  5. Department of Pharmacy, Cleveland Clinic Abu Dhabi, Abu Dhabi, UAE.
  6. Center for Brain and Nervous System Diseases (Neurocenter), Genolier Swiss Medical Network (Geneva, Lausanne, Glion, Genolier, Fribourg, Zurich), Clinique Valmont, 1823, Glion/Montreux, Switzerland.

PMID: 34893967 PMCID: PMC8664670 DOI: 10.1007/s13318-021-00743-8

Abstract

Desmoteplase is a bat (Desmodus rotundus) saliva-derived fibrinolytic enzyme resembling a urokinase and tissue plasminogen activator. It is highly dependent on fibrin and has some neuroprotective attributes. Intravenous administration of desmoteplase is safe and well tolerated in healthy subjects. Plasma fibrinolytic activity is linearly related to its blood concentration, its terminal elimination half-life ranges from 3.8 to 4.92 h (50 vs. 90 μg/kg dose). Administration of desmoteplase leads to transitory derangement of fibrinogen, D-dimer, alpha2-antiplasmin, and plasmin and antiplasmin complex which normalize within 4-12 h. It does not alter a prothrombin test, international normalized ratio, activated partial thromboplastin time, and prothrombin fragment 1.2. Desmoteplase was tested in myocardial infarction and pulmonary embolism and showed promising results versus alteplase. In ischemic stroke trials, desmoteplase was linked to increased rates of symptomatic intracranial hemorrhages and case fatality. However, data from "The desmoteplase in Acute Ischemic Stroke" Trials, DIAS-3 and DIAS-J, suggest that the drug is well tolerated and its safety profile is comparable to placebo. Desmoteplase is theoretically a superior thrombolytic because of high fibrin specificity, no activation of beta-amyloid, and lack of neurotoxicity. It was associated with better outcomes in patients with significant stenosis or occlusion of a proximal precerebral vessels. However, DIAS-4 was stopped as it might have not reached its primary endpoint. Due to its promising properties, desmoteplase may be added into treatment of ischemic stroke with extension of the time window and special emphasis on patients presenting outside the 4.5-h thrombolysis window, with wake-up strokes and strokes of unknown onset.

© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.

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