Argatroban

Structural formula
General
Non-proprietary name	Argatroban
other names	(2 R , 4 R ) -1 - [(2 S ) -5- (diaminomethylideneamino) -2 - {[(3 R ) -3-methyl-1,2,3,4-tetrahydroquinolin-8-yl] sulfonylamino } pentanoyl] -4-methyl-piperidine-2-carboxylic acid ( IUPAC )
Molecular formula	C 23 H 36 N 6 O 5 S
External identifiers / databases
EC number	638-764-8
ECHA InfoCard	100.166.378
PubChem	152951
ChemSpider	134807
DrugBank	DB00278
Wikidata	Q474880
Drug information
ATC code	B01 AE03
Drug class	Anticoagulants
Mechanism of action	Thrombin - inhibitor
properties
Molar mass	508.635 g · mol -1
safety instructions
	Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS labeling of hazardous substances	no GHS pictograms
	no GHS pictograms
H and P phrases	H: no H-phrases
	P: no P-phrases
	As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Argatroban is a drug used to inhibit blood clotting . The synthetic direct inhibitor of thrombin has been approved in Germany and Austria since 2005 under the name Argatra for anticoagulation in adults with heparin-induced thrombocytopenia of type II (HIT II), if they require parenteral antithrombotic therapy.

Chemically, argatroban is one of the non-peptide thrombin inhibitors. Both the monohydrate and the anhydrous form are used medicinally.

Mechanism of action

Argatroban belongs to the class of direct thrombin inhibitors (DTIs). The substance is a highly effective, monovalent direct thrombin inhibitor that selectively binds to the active catalytic binding site of the thrombin. Binding occurs to both dissolved and fibrin-bound (clot-bound) thrombin.

The anticoagulant effect of argatroban is based on the reversible inhibition of all effects of thrombin including fibrin formation , the activation of coagulation factors V, VIII and XIII as well as platelet activation and aggregation. It also inhibits the activation of protein C by thrombin.

Clinical information

Application areas (indications)

Argatroban has been approved under the trade name Argatra 100 mg / ml concentrate for the preparation of an infusion solution in Germany and Austria since 2005 for anticoagulation in adult patients with heparin-induced thrombocytopenia type II (HIT II) who require parenteral antithrombotic therapy. There are also individual case reports on use in children without approval.

dosage

The dosage depends on the individual condition of the patient. The dose may need to be reduced, especially in patients with impaired liver function. For postoperative patients, the manufacturer suggests a dose of 0.05 to 0.1 µg / kg * min as a continuous running rate (per perfusor ). The anticoagulation can be monitored with the activated partial thromboplastin time ( aPTT ). The target aPTT is 50–60 seconds.

metabolism

Argatroban has advantageous pharmacokinetics with a β- elimination half-life of 40 to 50 minutes, is broken down in the liver , mainly excreted in the bile and does not accumulate in patients with renal insufficiency .

Web links

MEROPS : Page to Argatroban

Individual evidence

↑ Data sheet Argatroban monohydrate from Sigma-Aldrich , accessed on December 3, 2018 ( PDF ).
↑ G. Geisslinger et al .: Mutschler drug effects . 11th edition. WVG, Stuttgart 2019, p. 484 .
↑ Thrombin inhibitors on Pschyrembel -Online; accessed on March 28, 2020.
↑ External identifiers or database links for argatroban monohydrate : CAS number: 141396-28-3, EC number: 687-500-8, ECHA InfoCard: 100.213.407 , PubChem : 92721 , Wikidata : Q59400516 .
^ Entry on Argatroban in the DrugBank of the University of Alberta , accessed December 3, 2018.
↑ Argatroban for heparin intolerance. In: Viennese clinical magazine. 17, 2014, p. 42, doi : 10.1007 / s00740-014-0221-0 .
^ S. Kleinschmidt, B. Stephan, G. Pindur, C. Bauer: Argatroban. In: The anesthesiologist. 55, 2006, p. 443, doi : 10.1007 / s00101-005-0962-7 .

[Sigma-1] Data sheet Argatroban monohydrate from Sigma-Aldrich , accessed on December 3, 2018 ( PDF ).

[2] G. Geisslinger et al .: Mutschler drug effects . 11th edition. WVG, Stuttgart 2019, p. 484 .

[3] Thrombin inhibitors on Pschyrembel -Online; accessed on March 28, 2020.

[4] External identifiers or database links for argatroban monohydrate : CAS number: 141396-28-3, EC number: 687-500-8, ECHA InfoCard: 100.213.407 , PubChem : 92721 , Wikidata : Q59400516 .

[5] Entry on Argatroban in the DrugBank of the University of Alberta , accessed December 3, 2018.

[6] Argatroban for heparin intolerance. In: Viennese clinical magazine. 17, 2014, p. 42, doi : 10.1007 / s00740-014-0221-0 .

[7] S. Kleinschmidt, B. Stephan, G. Pindur, C. Bauer: Argatroban. In: The anesthesiologist. 55, 2006, p. 443, doi : 10.1007 / s00101-005-0962-7 .