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Pharmacodynamic Properties of the Low Molecular Weight Heparin, Tinzaparin: Effect of Molecular Weight Distribution on Plasma Tissue Factor Pathway Inhibitor in Healthy Human Subjects

From Albany College of Pharmacy & PRI at Albany College of Pharmacy, Albany, New York (Dr. Mousa, Mr. Bozarth), and the Clinical Pharmacology and Therapeutics Division, Children's Hospital of Philadelphia (Dr. Barrett).

Low molecular weight heparins (LMWHs) stimulate the release of endothelial tissue factor pathway inhibitor (TFPI). An inhibitor of tissue factor-induced coagulation, TFPI may contribute to the efficacy of LMWHs. The release of TFPI may be affected by characteristics of LMWHs, such as molecular weight (MW) distribution. The authors measured plasma levels of TFPI after single, subcutaneous injections of tinzaparin (mean MW = 6500 Daltons [Da]; 3.5% of fractions < 2000 Da) or a tinzaparin-like LMWH (mean MW = 5650 Da; 18.3% of fractions < 2000 Da) in 30 healthy subjects. Maximum mean plasma levels of TFPI approached 200 to 230 ng/mL 0.8 hours after administration of either drug. Plasma levels of TFPI remained elevated compared with baseline values for 12 to 16 hours after drug administration. These results suggest that LMWH fractions < 2000 Da do not affect the release of TFPI.

Key Words: Tinzaparin • tissue factor pathway inhibitor • anti-Xa • anti-IIa • low molecular weight heparins • molecular weight fractions • pharmacodynamic

Address for reprints: Shaker A. Mousa, PhD, 106 New Scotland Avenue, Albany, NY 12208-3492.

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