CLINICAL PHARMACOKINETICS OF TICLOPIDINE

Platelets contribute significantly to arterial-occlusive thrombosis, o ne of the major causes of death and disease throughout the world. Cons equently, inhibiting platelet function is a potentially important ther apeutic goal. Among agents that inhibit platelet function, ticlopidine shows a wide spectrum of antiplatelet activity. There have been a lim ited number of studies investigating the pharmacokinetic profile of th e drug. However, it has been demonstrated that absorption of ticlopidi ne after oral administration is rapid, is improved when the drug is ad ministered with food, but reduced by the coadministration of antacid. Ticlopidine is extensively metabolised, with little unchanged drug pre sent in the plasma. After administration of a single dose, unchanged t iclopidine can be detected for up to 96 hours postdose. Repeated admin istration of ticlopidine 250mg twice daily results in 3- to 4-fold acc umulation of the drug after 2 weeks. The terminal elimination half-lif e is between 20 and 50 hours. Dosage selection is not determined by th e 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 i ncreased plasma drug concentrations. In contrast, the plasma concentra tion of cyclosporin is reduced. Aspirin (acetylsalicylic acid) increas es;he bleeding time in patients receiving ticlopidine concurrently, wh ile corticosteroids reduce bleeding time. Ticlopidine use is discourag ed in patients with severe organ failure. Furthermore, ticlopidine sho uld be discontinued 2 Weeks before surgery and dental intervention. Mo st importantly, the blood cell count should be monitored regularly dur ing the 3 first months of treatment with ticlopidine because 1% of pat ients receiving ticlopidine may experience agranulocytosis.