Danaparoid has a pharmacokinetic profile different from that of UFH or LMWH. It is well absorbed after subcutaneous (sc) administration, with its bioavailability approaching 100% (Stiekema et al., 1989; Danhof et al., 1992). In comparison, the bioavailability of LMWH is 87-92%, and that of UFH only 15-20% (Skoutakis, 1997). Danaparoid's plasma anti-Xa levels peak 4-5 h following sc injection (Danhof et al., 1992). Unlike heparins, it is not neutralized by plasma proteins, such as PF4 and histidine-rich glycoprotein, accounting for its high bioavailability after sc or intravenous (iv) administration. Danaparoid exhibits linear pharmacoki-netics and has relatively predictable plasma levels.

Danaparoid is eliminated mainly by the kidneys. It has a relatively long plasma anti-Xa half-life (t=2) of about 25 h. Plasma t=2 values of anti-IIa activity and TGI activity are much shorter, ranging from 2 to 4 h and 3 to 7 h, respectively (Bradbrook et al., 1987; Stiekema et al., 1989; Danhof et al., 1992). In patients with moderate to severe impairment of renal function the drug tends to accumulate, and the dose should be reduced in accordance with monitoring of plasma anti-Xa levels.

Danaparoid's metabolism is not affected by hepatic cytochrome P-450, nor does it affect hepatic or renal handling of other drugs. It has no significant effect on the pharmacodynamics and pharmacokinetics of coumarins. Its pharmacokinetics are not modified by age or body weight (Stiekema et al., 1989; Danhof et al., 1992).

There is no antidote for danaparoid (Stiekema et al., 1989). Protamine chloride only minimally neutralizes its anticoagulant activity. If severe bleeding occurs, the drug should be stopped and blood product replacement given, as indicated clinically. There is limited evidence that plasmapheresis can accelerate drug elimination (Schmahl et al., 1997), but this option is seldom practical.

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