Of the numerous biological effects of low molecular weight heparin, in clinical terms its action on blood coagulation is the most important. Reviparin is involved in different phases of blood coagulation. Because of its marked inhibitory action on factor Xa and comparatively low level of anti IIa activity, low molecular weight heparin is at its most active during the preliminary stages of coagulation. Reviparin’s ratio of anti Xa activity to anti IIa activity is 3.6–6.1 in vitro (the ratio for unfractionated heparin is 1).
With subcutaneous injection of reviparin the plasma levels peak after 3 hours then plateau and start to decline at 4-6 h after administration. Pharmacokinetic studies in 24 healthy subjects performed with reviparin demonstrated that a single subcutaneous dose of reviparin 1432 IU anti-Xa/0.25ml led to a mean Cmax (measured as anti-Xa-activity) of 0.14±0.03 IU/ml. Similar studies performed with higher doses of reviparin, indicate that the mean Cmax of reviparin increases with increase in dose.
The elimination half-life of subcutaneous reviparin is about 3 h, total clearance about 18 ml/min and the volume of distribution about 5 litres and are independent of dose. The compound is excreted mainly in the urine. The pharmacokinetic parameters with respect to anti-Xa activity and anti-IIa activity are virtually identical.
After subcutaneous administration the bioavailability of reviparin is about 95%. Studies in healthy subjects have not shown any major inter-individual variation of the bioavailability.
No studies have been performed to establish an appropriate dose of reviparin in patients with renal impairment. However, as the mechanism of clearance is predominantly renal, elimination may be delayed depending on the severity of renal dysfunction. Patients with renal impairment are expected to have increased exposure (AUC) and longer half-life compared to patients with normal renal function.
Toxicity, especially bleeding, occurs at dose levels considerably higher than the recommended dose and is related to the exaggerated pharmacodynamic effects of overdosing.
Studies with heparin and other low molecular weight heparins have shown osteoporotic effects, development of cataract and delayed healing of fractures and recalcification of the skeleton. It is not known if reviparin shows similar effects.
Studies of toxicity to reproduction and genotoxicity reveal no special hazard for humans. No carcinogenicity studies have been performed.
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