Metabolism of Fondaparinux

Fondaparinux is excreted unchanged in the urine without undergoing any metabolism in the body. 1

Pharmacokinetic Properties

Fondaparinux is a synthetic pentasaccharide with a molecular weight of 1,728 Da that selectively inhibits Factor Xa by binding to antithrombin III 1, 2
After subcutaneous injection, fondaparinux is rapidly and completely absorbed with 100% bioavailability 1, 3
Peak plasma concentration is reached approximately 2-3 hours after subcutaneous administration 1, 2
The terminal half-life is 17 hours in young subjects and extends to 21 hours in elderly patients 1, 2
Fondaparinux exhibits linear pharmacokinetics when given in subcutaneous doses of 2-8 mg or intravenous doses of 2-20 mg 1
Steady state is reached after the third or fourth once-daily dose 1, 2

Fondaparinux distributes mainly in blood with an apparent volume of distribution of 7-11 L 1
It is highly and specifically bound (at least 94%) to antithrombin III 1
Unlike heparin, fondaparinux has minimal nonspecific binding to other plasma proteins, including platelet factor 4 (PF4) 1, 2
This specific binding profile explains why fondaparinux has a low risk of heparin-induced thrombocytopenia 2

In individuals with normal kidney function, up to 77% of a single subcutaneous or intravenous fondaparinux dose is eliminated in urine as unchanged drug within 72 hours 1
Fondaparinux is not metabolized in vivo, as the majority of the administered dose is eliminated unchanged in urine 1
Unlike low molecular weight heparins, fondaparinux undergoes no hepatic metabolism 1, 3

Renal impairment: Fondaparinux elimination is significantly prolonged in patients with renal impairment 1
- Total clearance is approximately 25% lower in mild renal impairment (CrCl 50-80 mL/min) 1
- Total clearance is approximately 40% lower in moderate renal impairment (CrCl 30-50 mL/min) 1
- Total clearance is approximately 55% lower in severe renal impairment (CrCl <30 mL/min) 1
- Fondaparinux is contraindicated in patients with severe renal insufficiency (CrCl <30 mL/min) 2, 1
Elderly patients: Fondaparinux clearance is approximately 25% lower in patients older than 75 years compared to patients younger than 65 years 1, 2
Low body weight: Total clearance is decreased by approximately 30% in patients weighing less than 50 kg 1
- Fondaparinux is contraindicated for thromboprophylaxis in patients weighing less than 50 kg undergoing orthopedic or abdominal surgery 2

The predictable pharmacokinetics and lack of metabolism make fondaparinux dosing more straightforward compared to agents that undergo hepatic metabolism 3, 4
Dose adjustments are primarily needed based on renal function and body weight, not hepatic function 1, 2
The long half-life allows for convenient once-daily dosing 1, 3
Unlike heparin, fondaparinux does not bind to protamine sulfate, so this cannot be used as an antidote in case of bleeding 2
Fondaparinux-specific anti-Xa assays should be used when monitoring is required, as standard assays calibrated with heparin or LMWH are not appropriate 1, 2

Unlike heparin and low molecular weight heparins, fondaparinux has no metabolism and is exclusively eliminated by renal excretion 1, 4
Fondaparinux has a longer half-life (17-21 hours) compared to low molecular weight heparins (approximately 4 hours) 2, 3
Fondaparinux has minimal nonspecific binding compared to heparin and low molecular weight heparins, resulting in more predictable pharmacokinetics 1, 2