Animal pharmacokinetics of inogatran, a low-molecular-weight thrombin inhibitor with potential use as an antithrombotic drug

1998 ◽  
Vol 19 (1) ◽  
pp. 55-64 ◽  
Author(s):  
Ulf G. Eriksson ◽  
Lars Renberg ◽  
Ulf Bredberg ◽  
Ann-Catrine Teger-Nilsson ◽  
Carl Gunnar Regårdh
Keyword(s):  
Molecular Weight ◽  
Thrombin Inhibitor ◽  
Low Molecular Weight ◽  
Antithrombotic Drug ◽  
Potential Use ◽  
Animal Pharmacokinetics

Antithrombotic Effect of Two Low Molecular Weight Thrombin Inhibitors and a Low-Molecular Weight Heparin in a Caval Vein Thrombosis Model in the Rat

1997 ◽  
Vol 78 (05) ◽  
pp. 1404-1407 ◽  
Author(s):  
B I Eriksson ◽  
S Carlsson ◽  
M Halvarsson ◽  
B Risberg ◽  
C Mattsson
Keyword(s):  
Molecular Weight ◽  
Low Molecular Weight Heparin ◽  
Clinical Situation ◽  
Thrombin Inhibitors ◽  
Thrombin Inhibitor ◽  
Low Molecular Weight ◽  
Surgical Trauma ◽  
Antithrombotic Effect ◽  
Caval Vein ◽  
Thrombosis Model

SummaryA sensitive thrombosis model with a high reproducibility was developed in the rat, utilizing stasis of the caval vein and a standardized surgical trauma as the only thrombogenic stimuli. Since no procoagulant substances were used, the results of the present study might be relevant in a clinical situation. The antithrombotic effect of two recently synthesized low-molecular-weight thrombin inhibitors have been compared to dalteparin, (Fragmin) a low-molecular-weight heparin fragment. Each compound was studied at 8 different doses with 10 rats in each group. On a gravimetric basis, the thrombin inhibitor melagatran was twice as potent as dalteparin (ED50 16 and 33 µ/kg per h, respectively). The second thrombin inhibitor, inogatran, had an intermediate effect, with an ED50 of 24 µLg/kg per h. No differences in antithrombotic effect were, however, found when the compounds were compared at anticoagulant equivalent doses (same APTT prolongation). A 50% reduction in the mean thrombus weight was obtained when APTT was prolonged to 1.2 to 1.3 times the pretreatment value.

Liposome coated with low molecular weight chitosan and its potential use in ocular drug delivery

2009 ◽  
Vol 379 (1) ◽  
pp. 131-138 ◽  
Author(s):  
Ning Li ◽  
Chunyang Zhuang ◽  
Mi Wang ◽  
Xiyang Sun ◽  
Shufang Nie ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Molecular Weight ◽  
Ocular Drug Delivery ◽  
Low Molecular Weight ◽  
Low Molecular Weight Chitosan ◽  
Potential Use

Melagatran, a Low Molecular Weight Thrombin Inhibitor, Counteracts Endotoxin-induced Haemodynamic and Renal Dysfunctions in the Pig

1998 ◽  
Vol 80 (12) ◽  
pp. 1022-1026 ◽  
Author(s):  
Anders Larsson ◽  
Tom Saldeen ◽  
Christer Mattsson ◽  
Mats Eriksson
Keyword(s):  
Molecular Weight ◽  
Septic Shock ◽  
Resistance Index ◽  
Left Ventricular ◽  
Thrombin Inhibitor ◽  
Low Molecular Weight ◽  
Stroke Work ◽  
Work Index ◽  
Stroke Work Index ◽  
Ventricular Stroke Work Index

SummaryCoagulation and fibrinolysis are crucial in septic shock and inhibition of thrombin may be beneficial in this circumstance. Since porcine endotoxaemia has been found to replicate severe septic shock, a low molecular weight thrombin inhibitor, melagatran, was infused during the first 3 out of 6 h of endotoxaemia in pigs. Plasma creatinine (p <0.01) and urinary output (p <0.05) were less affected in the melagatran + endotoxin group (n = 6) as compared to endotoxaemic controls (n = 9). The left ventricular stroke work index, systemic vascular resistance index and oxygen extraction were all less affected (p <0.05) by endotoxin during the infusion of melagatran. The plasma concentration of melagatran declined with an apparent plasma half-life of 5 h as soon as the infusion was stopped. APTT, however, continued to increase after the infusion of melagatran had stopped and reached a maximum of 113 s at 5 h (baseline 17 s). APTT in endotoxaemic control pigs reached a maximum of 22 s. Thus, melagatran may counteract some consequences of endotoxaemia.

IN VITRO EFFECTS OF INOGATRAN, A SELECTIVE LOW MOLECULAR WEIGHT THROMBIN INHIBITOR

1997 ◽  
Vol 85 (2) ◽  
pp. 133-145 ◽  
Author(s):  
Ann-Catrine Teger-Nilsson ◽  
Ruth Bylund ◽  
David Gustafsson ◽  
Erika Gyzander ◽  
Ulf Eriksson
Keyword(s):  
Molecular Weight ◽  
Thrombin Inhibitor ◽  
Low Molecular Weight ◽  
In Vitro Effects

Interspecies Pharmacokinetic Comparisons and Allometric Scaling of Napsagatran, a Low Molecular Weight Thrombin Inhibitor

1999 ◽  
Vol 51 (1) ◽  
pp. 85-91 ◽  
Author(s):  
Thierry Lavé ◽  
Renée Portmann ◽  
Gabriela Schenker ◽  
Alvaro Gianni ◽  
Alberto Guenzi ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Allometric Scaling ◽  
Thrombin Inhibitor ◽  
Low Molecular Weight

scholarly journals Hyaluronan is abundant in COVID-19 respiratory secretions

2020 ◽  
Author(s):  
Gernot Kaber ◽  
Michael J. Kratochvil ◽  
Elizabeth B Burgener ◽  
Egan L Peltan ◽  
Graham Barlow ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Molecular Weight ◽  
Extracellular Matrix ◽  
Respiratory Infections ◽  
Therapeutic Strategies ◽  
Low Molecular Weight ◽  
Healthy Controls ◽  
Active Inflammation ◽  
Sample Set ◽  
Potential Use

COVID-19 respiratory infections are associated with copious, adherent respiratory secretions that prolong chronic ventilation and contribute to the morbidity and mortality caused by the disease. We hypothesized that hyaluronan, an extracellular matrix glycosaminoglycan produced at sites of active inflammation that promotes edema in other settings, might be a component of these secretions. To interrogate this, we examined the respiratory secretions collected from eight intubated patients with COVID-19, six control patients with cystic fibrosis (CF), a different respiratory disease also associated with thick adherent secretions, and eight healthy controls. In this sample set we found that hyaluronan content is increased approximately 20-fold in both CF and COVID-19 patients compared to healthy controls. The hyaluronan in COVID-19 samples was comprised of low-molecular weight fragments, the hyaluronan form most strongly linked with pro-inflammatory functions. Hyaluronan is similarly abundant in histologic sections from cadaveric lung tissue from COVID-19 patients. These findings implicate hyaluronan in the thick respiratory secretions characteristic of COVID-19 infection. Therapeutic strategies targeting hyaluronan should be investigated further for potential use in patients with COVID-19.

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