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Pharmacotherapeutic group: antithrombotic agent, heparin group. Antithrombotic. ATC code: B01AB12.
Pharmacology: Pharmacodynamics: Bemiparin sodium is a LMWH obtained by depolymerization of heparin sodium from porcine intestinal mucosa. Its mean molecular weight (MW) is approximately 3,600 daltons. The percentage of chains with MW lower than 2,000 daltons is less than 35%. The percentage of chains with MW from 2,000 to 6,000 daltons ranges between 50-75%. The percentage of chains with MW higher than 6,000 daltons is less than 15%.
The anti-Xa activity ranges between 80 and 120 anti-Xa IU per mg and the anti-IIa activity ranges between 5 and 20 anti-IIa IU per mg, calculated in relation to dry matter. The anti-Xa/anti-IIa ratio is approximately 8.
In animal experiment models, bemiparin has shown antithrombotic activity and moderate haemorrhagic effect.
In humans, bemiparin has confirmed its antithrombotic activity and, at the recommended doses, it does not significantly prolong global clotting tests.
Pharmacokinetics: The pharmacokinetic properties of bemiparin have been determined by measuring the plasma anti-Xa activity using the amydolitic method; it is based on reference to the W.H.O. First International Low Molecular Weight Heparin Reference Standard LMWH (NIBSC).
The absorption and elimination processes follow a linear kinetic of the 1st order.
Absorption: Bemiparin sodium is rapidly absorbed following subcutaneous injection and the bioavailability is estimated to be 96%. The maximum plasma anti-Xa effect at prophylactic doses of 2,500 IU and 3,500 IU occurs 2 to 3 hours after subcutaneous injection of bemiparin, reaching peak activities in the order of 0.34 ± (0.08) and 0.45 ± (0.07) IU anti-Xa/ml, respectively. Anti-IIa activity was not detected at these doses. The maximum plasma anti-Xa effect at treatment doses of 5,000 IU, 7,500 IU, 10,000 IU and 12,500 IU occurs 3 to 4 hours after subcutaneous injection of bemiparin, reaching peak activities in the order of 0.54 ± (0.06), 1.22 ± (0.27), 1.42 ± (0.19) and 2.03 ± (0.25) IU anti-Xa/ml, respectively. Anti-IIa activity of 0.01 IU/ml was detected at doses of 7,500 IU, 10,000 IU and 12,500 IU.
Elimination: Bemiparin administered in the dose range of 2,500 IU to 12,500 IU has an approximate half-life of between 5 and 6 hours, and should therefore be administered once daily.
There are currently no data available with regards to plasma protein binding, metabolism and excretion of bemiparin in humans.
Toxicology: Preclinical safety data: Preclinical data for bemiparin reveal no special hazard for humans based on conventional studies of safety pharmacology, single and repeated dose toxicity, genotoxicity and reproduction toxicity.
Acute and repeated dose toxicity studies following subcutaneous administration of bemiparin in animals have revealed alterations consisting essentially in reversible, dose-dependent haemorrhagic lesions at the injection site. These were considered to result from exaggerated pharmacological activity.
In the studies of reproductive toxicity performed with bemiparin in pregnant rats and rabbits, between days 6 and 18 of the pregnancy, no mortality was recorded among the females treated with bemiparin. The main clinical signs recorded were subcutaneous haematomas that were attributable to a pharmacological effect of the test item. No treatment-related embryotoxic effect neither external, skeletal and/or visceral alterations were recorded in the examination of fetuses.
