*3.1.3. Pharmacokinetics*

Heparin is not absorbed orally and therefore is administered parenterally. The two preferred routes of administration are continuous intravenous infusion or subcutaneous injection. If administered subcutaneously, the dose of heparin should be higher than the usual intravenous dose because subcutaneous administration is associated with reduced bioavailability [46]. UFH does not have predictable pharmacokinetics, and it has a small volume of distribution and a relatively short half-life of about 0.5–1 hour [47]. After injection heparin rapidly disappears from blood: the rapid, saturable elimination phase is thought to reflect UFH binding to vascular endothelial cells, macrophages, and reticuloendothelial cells, where it is internalized and metabolized into smaller and less sulfated forms [48]. At higher doses, the cellular binding sites are saturated, and heparin is cleared predominantly by renal elimination [49]. UFH binds also to plasma proteins, changing its pharmacokinetic profile and reducing its anticoagulant activity. Because of the unpredictable anticoagulant response, careful/close monitoring is essential, when UFH is given in therapeutic doses [48].

LMWHs do not bind to endothelial cells, macrophages, or reticuloendothelial cells and have a 2–4 times longer half-life compared to UFH (3–6 hours). Furthermore, LMWHs have much lower affinity for heparin-binding plasma proteins and are mainly removed by nonsaturable renal filtration, and thus, their clearance is independent of dose and plasma concentration [50].
