Identification

Name
Desirudin
Accession Number
DB11095
Type
Biotech
Groups
Approved
Biologic Classification
Protein Based Therapies
Other protein based therapies
Description

Desirudin is a direct inhibitor of human thrombin. It has a protein structure that is similar to that of hirudin, the naturally occurring anticoagulant present in the peripharyngeal glands in the medicinal leech, Hirudo medicinalis. Hirudin is a single polypeptide chain of 65 amino acids residues and contains three disulfide bridges. Desirudin has a chemical formula of C287H440N80O110S6 with a molecular weight of 6963.52.

It is mainly indicated for the prevention of deep vein thrombosis in hip replacement surgery patients. Common side effects include: Bleeding gums, collection of blood under the skin, coughing up blood, deep, dark purple bruise and difficulty with breathing or swallowing.

Protein chemical formula
C287H440N80O110S6
Protein average weight
Not Available
Sequences
Not Available
Synonyms
  • 63-Desulfohirudin
  • 63-Desulfohirudin (Hirudo Medicinalis Isoform HV1)
  • 63-Desulfohirudin (recombinant)
  • Desirudin recombinant
  • Desirudina
  • Hirudin desirudin
External IDs
CGP-39393
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
IprivaskInjection, powder, lyophilized, for solution15 mg/100mgSubcutaneousCanyon Pharmaceuticals, Inc.2010-06-102010-11-01Us
IprivaskKit30 mg/1mLMarathon Pharmaceuticals2013-12-312016-08-31Us
IprivaskKit30 mg/1mLSubcutaneousCANYON PHARMACEUTICALS, INC2010-08-302014-05-09Us
IprivaskKit30 mg/1mLValeant Pharmaceuticals North America2013-12-312018-10-11Us
Categories
UNII
U0JZ726775
CAS number
120993-53-5

Pharmacology

Indication

Indicated as prophylaxis of deep vein thrombosis for patients undergoing hip replacement surgery.

Associated Conditions
Pharmacodynamics

Desirudin results in dose-dependent prolongation of the activated partial thromboplastin time (aPTT).

Mechanism of action

Desirudin is a direct, highly selective thrombin inhibitor. Reversibly binds to the active thrombin site of free and clot-associated thrombin. Inhibits fibrin formation, activation of coagulation factors V, VII, and XIII, and thrombin-induced platelet aggregation resulting in a dose-dependent prolongation of the activated partial thromboplastin time (aPTT).

Absorption

Absorption is complete after subcutaneous administration. Time to peak in plasma is 1 to 3 hours.

Volume of distribution

0.25 L/kg.

Protein binding

Desirudin binds specifically and directly to thrombin, forming an extremely tight, non-covalent complex with an inhibitionconstant of approximately 2.6 x 10-13 M. Thus, free or protein bound desirudin immediately binds circulating thrombin.

Metabolism

Human and animal data suggest that desirudin is primarily eliminated and metabolized by the kidney. The total urinary excretion of unchanged desirudin amounts to 40 to 50% of the administered dose. Metabolites lacking one or two C-terminal amino acids constitute a minor proportion of the material recovered from urine (< 7%). There is no evidence for the presence of other metabolites. This indicates that desirudin is metabolized by stepwise degradation from the C-terminus probably catalyzed by carboxypeptidase(s) such as carboxypeptidase A.

Route of elimination

Urine (40% to 50% as unchanged drug).

Half life

~2 hours.

Clearance

1.5 to 2.7 mL/min/kg.

Toxicity

No data available.

Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(1,2,6,7-3H)TestosteroneThe therapeutic efficacy of Desirudin can be increased when used in combination with (1,2,6,7-3H)Testosterone.
(R)-warfarinThe risk or severity of bleeding can be increased when Desirudin is combined with (R)-warfarin.
(S)-WarfarinThe risk or severity of bleeding can be increased when Desirudin is combined with (S)-Warfarin.
1-TestosteroneThe therapeutic efficacy of Desirudin can be increased when used in combination with 1-Testosterone.
18-methyl-19-nortestosteroneThe therapeutic efficacy of Desirudin can be increased when used in combination with 18-methyl-19-nortestosterone.
4-hydroxycoumarinThe risk or severity of bleeding can be increased when Desirudin is combined with 4-hydroxycoumarin.
4-HydroxytestosteroneThe therapeutic efficacy of Desirudin can be increased when used in combination with 4-Hydroxytestosterone.
5beta-dihydrotestosteroneThe therapeutic efficacy of Desirudin can be increased when used in combination with 5beta-dihydrotestosterone.
AbciximabThe risk or severity of bleeding can be increased when Abciximab is combined with Desirudin.
AceclofenacThe risk or severity of bleeding and hemorrhage can be increased when Aceclofenac is combined with Desirudin.
Food Interactions
Not Available

References

General References
  1. Monograph [Link]
  2. FDA label [Link]
External Links
PubChem Substance
347911114
Wikipedia
Desirudin
ATC Codes
B01AE01 — Desirudin

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2, 3CompletedPreventionDeep Venous Thrombosis1
4CompletedTreatmentThrombotic events1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
Injection, powder, lyophilized, for solutionSubcutaneous15 mg/100mg
Kit30 mg/1mL
KitSubcutaneous30 mg/1mL
Prices
Not Available
Patents
Not Available

Properties

State
Not Available
Experimental Properties
Not Available

Taxonomy

Description
Not Available
Kingdom
Organic Compounds
Super Class
Organic Acids
Class
Carboxylic Acids and Derivatives
Sub Class
Amino Acids, Peptides, and Analogues
Direct Parent
Peptides
Alternative Parents
Not Available
Substituents
Not Available
Molecular Framework
Not Available
External Descriptors
Not Available

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Zinc ion binding
Specific Function
Carboxypeptidase that catalyzes the release of a C-terminal amino acid, but has little or no action with -Asp, -Glu, -Arg, -Lys or -Pro.
Gene Name
CPA1
Uniprot ID
P15085
Uniprot Name
Carboxypeptidase A1
Molecular Weight
47139.86 Da

Drug created on December 03, 2015 09:51 / Updated on November 05, 2018 17:49