Description

CLINICAL PHARMACOLOGY 
Heparin inhibits reactions that lead to the clotting of blood and the formation of fibrin clots both in 
vitro and in vivo. Heparin acts at multiple sites in the normal coagulation system. Small amounts of 
heparin in combination with antithrombin III (heparin cofactor) can inhibit thrombosis by inactivating 

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NDA 17-037/S-158 
Page 24 
activated Factor X and inhibiting the conversion of prothrombin to thrombin. Once active thrombosis 
has developed, larger amounts of heparin can inhibit further coagulation by inactivating thrombin and 
preventing the conversion of fibrinogen to fibrin. Heparin also prevents the formation of a stable fibrin 
clot by inhibiting the activation of the fibrin stabilizing factor. 
Bleeding time is usually unaffected by heparin. Clotting time is prolonged by full therapeutic doses of 
heparin; in most cases, it is not measurably affected by low doses of heparin. Loglinear plots of 
heparin plasma concentrations with time, for a wide range of dose levels, are linear, which suggests the 
absence of zero order processes. Liver and the reticulo-endothelial system are the sites of 
biotransformation. The biphasic elimination curve, a rapidly declining alpha phase (t
1/2
= 10 min), and 
after the age of 40 a slower beta phase, indicates uptake in organs. The absence of a relationship 
between anticoagulant half-life and concentration half-life may reflect factors such as protein binding 
of heparin. 
Patients over 60 years of age, following similar doses of heparin, may have higher plasma levels of 
heparin and longer activated partial thromboplastin times (APTTs) compared with patients under 60 
years of age. 
Heparin does not have fibrinolytic activity; therefore, it will not lyse existing clots. 
INDICATIONS AND USAGE 
HEP-LOCK U/P (Preservative-Free Heparin Lock Flush Solution, USP) is intended to maintain 
patency of an indwelling venipuncture device designed for intermittent injection or infusion therapy or 
blood sampling. Heparin Lock Flush Solution may be used following initial placement of the device in 
the vein, after each injection of a medication or after withdrawal of blood for laboratory tests. (See