innohep Mechanism of Action

Properties: Tinzaparin sodium is a low molecular weight heparin of porcine origin with an anti-Xa/anti-IIa ratio between 1.5 and 2.5. Tinzaparin sodium is produced by enzymatic depolymerization of conventional unfractionated heparin. Like conventional heparin, Tinzaparin sodium acts as an anticoagulant by potentiating Antithrombin III's inhibition of activated coagulation factors, primarily factor Xa.
The biological activity of tinzaparin sodium is standardized against the 1st "International standards for low molecular weight heparins", and expressed in anti-Xa international units (IU).
The anti-Xa activity of tinzaparin sodium is not less than 70 and not more than 120 IU/mg.
The characteristic value of the mass-average molecular mass of tinzaparin sodium is about 6,500.
The mass percentage of chains lower than 2,000 is not more than 10.0 percent. The mass percentage of chains between 2,000 and 8,000 ranges between 60.0 and 72.0 percent (typical 66%). The mass percentage of chains above 8,000 ranges between 22.0 and 36.0 percent.
The maximum anti-Xa activity is seen after 4-6 hours following subcutaneous injection. The elimination half-life of anti-Xa activity after i.v. injection is approx. 90 minutes. Bioavailability of anti-Xa activity is 90%. Due to the very long biological half-life of Tinzaparin sodium (innohep), administration once daily is sufficient.
Tinzaparin undergoes minor metabolization in the liver through a depolymerization and is excreted via the kidneys as an unchanged or almost unchanged form. The pharmacokinetic activities of Tinzaparin sodium (innohep) have been studied in pregnancy.
Data from sequential pharmacokinetic monitoring in 55 pregnancies suggests that pharmacokinetic properties do not differ from the non-pregnant state. There was a small, but non-statistically significant, decrease in anti-Xa levels with advancing gestation. Some monitoring of peak anti-Xa levels four hours following administration of tinzaparin is recommended in the first weeks of administration and in late pregnancy.
Toxicology: Preclinical Safety Data: Heparins and LMW-heparins are generally only slightly toxic, and this applies for tinzaparin sodium as well. The most important effect observed in studies of acute, sub-acute and chronic toxicity, reproduction toxicity and mutagenicity is haemorrhaging caused by the very high doses administered.
After intramuscular administration of LMW-heparin in animals necrotising haematoma were observed. Osteoporotic effects were revealed in a 12-months study in rats. Animal studies in rats and rabbits failed to find a teratogenic potential of LMW-heparin in doses up to 25 mg/kg bodyweight. Foetuses which were prenatally exposed to 10 mg/kg body weight were found to have lower bodyweights than controls.