What is the half-life of argatroban (direct thrombin inhibitor)?

Argatroban Half-Life

Argatroban has a plasma half-life of 45 minutes in patients with normal hepatic function. 1

Half-Life in Normal Conditions

• The terminal elimination half-life of argatroban ranges between 39 and 51 minutes in patients with normal organ function 2, 3
• This short half-life allows for rapid onset of anticoagulant effect upon initiation and quick restoration of normal hemostasis upon discontinuation 3, 4
• The drug reaches steady-state within approximately 1-3 hours of continuous infusion 2

Half-Life in Hepatic Impairment

Hepatic dysfunction significantly prolongs argatroban's half-life, requiring substantial dose reduction. 1

• In patients with moderate hepatic insufficiency (Child-Pugh class B), the half-life increases to approximately 50 minutes at baseline, but can be multiplied by 3 with more severe impairment 5
• In patients with Child-Pugh score >6, the elimination half-life extends to 181 minutes (approximately 3 hours) 2
• When the Child-Pugh score exceeds 6, the half-life can increase from 50 to 152 minutes 1
• This prolongation occurs because argatroban is metabolized in the liver via the cytochrome P450 3A4/5 enzyme system 1, 6

Half-Life in Special Clinical Populations

In critically ill cardiac surgical patients, the median half-life is markedly prolonged to 2.7 hours (range 1.8-7.3 hours). 7

• The half-life in critically ill patients correlates significantly with total bilirubin concentration (R² = 0.66) 7
• Continuous veno-venous hemodialysis does not significantly affect argatroban plasma half-life 7
• Approximately 20% of argatroban is cleared through dialysis during a 4-hour hemodialysis session, but this does not substantially alter the half-life 2

Half-Life Compared to Other Direct Thrombin Inhibitors

• Bivalirudin has a shorter half-life of 20-30 minutes (or 25-36 minutes per some sources) 1
• Argatroban's half-life of 40-50 minutes is intermediate compared to other anticoagulants used in similar settings 1

Clinical Implications of Half-Life

• The relatively short half-life means anticoagulation parameters generally return to baseline within 2-4 hours after discontinuation 8
• For preoperative management, argatroban infusion should be stopped 4 hours before surgery to allow adequate clearance 1
• The short half-life eliminates the need for renal dose adjustment, as argatroban is not renally excreted 1, 6
• In ECMO patients, the pharmacokinetics may be altered, requiring substantially lower doses (0.2-0.5 μg/kg/min) despite the unchanged half-life 1