Detailed Product Description

Clopidogrel hydrogen sulfate is designated chemically as methyl (+)-(S)-(-(2-chlorophenyl)-6,7-dihydrothieno[3,2-c] pyridine-5(4H)-acetate sulfate (1:1).

The empirical formula of clopidogrel hydrogen sulfate is C₁₆H₁₆ClNO₂S. H₂SO₄ and its molecular weight is 419.9.

CAS Number: 120202-66-6 (Clopidogrel hydrogen sulfate),

113 665-84-2 (Clopidogrel base). Identification

Clopidogrel hydrogen sulfate is a white to off-white powder. It is practically insoluble in water at neutral pH but freely soluble at pH 1. It is freely soluble in methanol, sparingly soluble in methylene chloride and is practically insoluble in ethyl ether. It has a specific optical rotation of about + 56°.

Each tablet contains mannitol, macrogol 6000, microcrystalline cellulose, castor oil-hydrogenated, hydroxypropylcellulose. The coating contains lactose, hypromellose, titanium dioxide, glycerol triacetate, iron oxide red and carnauba wax.

Clopidogrel is a specific and potent inhibitor of platelet aggregation. Platelets have an established role in the pathophysiology of atherosclerotic disease and thrombotic events. Long term use of anti-platelet drugs has shown consistent benefit in the prevention of ischaemic stroke, myocardial infarction and vascular death in patients at increased risk of such outcomes, including those with established atherosclerosis or a history of atherothrombosis.

Clopidogrel selectively inhibits the binding of adenosine diphosphate (ADP) to its platelet receptor, and the subsequent ADP-mediated activation of the GPIIb/IIIa complex, thereby inhibiting platelet aggregation. Biotransformation of clopidogrel is necessary to produce inhibition of platelet aggregation. However, an active metabolite responsible for the activity of the drug has not been isolated. Clopidogrel also inhibits platelet aggregation induced by other agonists by blocking the amplification of platelet activation by released ADP.

Clopidogrel acts by irreversibly modifying the platelet ADP receptor. Consequently, platelets exposed to clopidogrel are affected for the remainder of their lifespan and recovery of normal platelet function occurs at a rate consistent with platelet turnover (approximately 7 days).

Statistically significant and dose-dependent inhibition of platelet aggregation was noted 2 hours after single oral doses of clopidogrel. Repeated doses of 75 mg per day produced substantial inhibition of ADP-induced platelet aggregation from the first day; this increased progressively and reached steady state between Day 3 and Day 7. At steady state, the average inhibition level observed with a dose of 75 mg per day was between 40% and 60%. Platelet aggregation and bleeding time gradually returned to baseline values, generally within 7 days after treatment was discontinued.

After repeated oral doses of 75 mg per day, a single oral dose of clopidogrel is rapidly absorbed. However, plasma concentrations of the parent compound are very low and below the quantification limit (0.00025 mg/L) beyond 2 hours. Absorption is at least 50%, based on urinary excretion of clopidogrel metabolites

Clopidogrel is extensively metabolised by the liver and the main metabolite, which is inactive, is the carboxylic acid derivative which represents about 85% of the circulating compound in plasma. Peak plasma levels of this metabolite (approx. 3 mg/L after repeated 75 mg oral doses) occurred approximately 1 hour after dosing.

The kinetics of the main circulating metabolite were linear (plasma concentrations increased in proportion to dose) in the dose range of 50 to 150 mg of clopidogrel.

Clopidogrel and the main circulating metabolite bind reversibly in vitro to human plasma proteins (98% and 94% respectively). The binding is non saturable in vitro over a wide concentration range.

Following an oral dose of ¹⁴C-labelled clopidogrel in man, approximately 50% was excreted in the urine and approximately 46% in the faeces in the 120 hour interval after dosing. The elimination half-life of the main circulating metabolite was 8 hours after single and repeated administration.

Plasma concentrations of the main circulating metabolite were significantly higher in elderly subjects (( 75 years) as compared to young healthy volunteers. However, these higher plasma levels were not associated with differences in platelet aggregation and bleeding time.

Plasma levels of the main circulating metabolite were lower in subjects with severe renal disease (creatinine clearance from 5 to 15 mL/min) compared to subjects with moderate renal disease (creatinine clearance from 30 to 60 mL/min) and healthy subjects, after repeated doses of 75 mg/day. Although inhibition of ADP-induced platelet aggregation was lower (25%) than that observed in healthy subjects, the prolongation of bleeding was similar to that seen in healthy subjects receiving 75 mg of clopidogrel per day.

Molecular formula: C16h16clno2s. H2so4
Description: White crystal powder
Content: 98. 5%

Package:  25kg/drum