Clinical Pharmacokinetics of Ticlopidine

Summary

Platelets contribute significantly to arterial-occlusive thrombosis, one of the major causes of death and disease throughout the world. Consequently, inhibiting platelet function is a potentially important therapeutic goal. Among agents that inhibit platelet function, ticlopidine shows a wide spectrum of antiplatelet activity.

There have been a limited number of studies investigating the pharmacokinetic profile of the drug. However, it has been demonstrated that absorption of ticlopidine after oral administration is rapid, is improved when the drug is administered with food, but reduced by the coadministration of antacid. Ticlopidine is extensively metabolised, with little unchanged drug present in the plasma. After administration of a single dose, unchanged ticlopidine can be detected for up to 96 hours postdose. Repeated administration of ticlopidine 250mg twice daily results in 3- to 4-fold accumulation of the drug after 2 weeks. The terminal elimination half-life is between 20 and 50 hours.

Dosage selection is not determined by the pharmacokinetic profile of the drug, but rather by determination of the effect of the drug on bleeding time. The clearance of theophylline and Phenazone (antipyrine) are reduced by ticlopidine, resulting in increased plasma drug concentrations. In contrast, the plasma concentration of cyclosporin is reduced. Aspirin (acetylsalicylic acid) increases the bleeding time in patients receiving ticlopidine concurrently, while corticosteroids reduce bleeding time.

Ticlopidine use is discouraged in patients with severe organ failure. Furthermore, ticlopidine should be discontinued 2 weeks before surgery and dental intervention. Most importantly, the blood cell count should be monitored regularly during the 3 first months of treatment with ticlopidine because 1% of patients receiving ticlopidine may experience agranulocytosis.