Special pharmacokinetics of dipetarudin suggests a potential antitumor activity of this thrombin inhibitor.
Thrombin is a potent mitogen for many tumor cells, suggesting that this enzyme may be involved in tumor genesis and metastasis. Inhibition of thrombin expressed on the surface of tumor cells may improve outcomes in some tumor cases. For this reason, a thrombin inhibitor to be applied in antitumor therapy must have favorable pharmacokinetic attributes to exert its action as long as possible in the extravascular compartment of the extracellular space, with a short action intravascularly, avoiding bleeding and/or other undesirable side-effects. None of the thrombin inhibitors in clinical use has these properties. Here, we report for first time a direct thrombin inhibitor, named dipetarudin that could be very useful in antitumor therapy because of its pharmacokinetic behavior characterized by a rapid distribution in the extravascular space with a slow elimination from this compartment.
López
Mercedes L
ML
Laboratorio de Trombosis Experimental, Centro de Biofisica y Bioquimica, Caracas, Venezuela. mercedesllz@hotmail.com
Nowak
Goetz
G
D000465:Algorithms; D000818:Animals; D000970:Antineoplastic Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D019540:Area Under Curve; D001682:Biological Availability; D004195:Disease Models, Animal; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D005110:Extracellular Space / Q000187:drug effects; D006207:Half-Life; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D009392:Nephrectomy / Q000379:methods; D051381:Rats; D017208:Rats, Wistar; D011993:Recombinant Fusion Proteins / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics* / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000493:pharmacokinetics / Q000627:therapeutic use; D013917:Thrombin / Q000037:antagonists & inhibitors* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D013997:Time Factors
D000970:Antineoplastic Agents; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; C493509:dipetarudin; D013917:Thrombin