Pharmacokinetics and Effect of Ticlopidine on Platelet Aggregation in Subjects with Normal and Impaired Renal Function

Abstract

The pharmacokinetics and the effect of ticlopidine on platelet aggregation were determined in patients with chronic renal failure (n = 6), who were not on dialysis and had glomerular filtration of 16.9 +/- 4.4 mL/min, and were matched with the pharmacokinetics and effects in healthy volunteers (n = 7). Participants were studied after acute oral administration of ticlopidine at the beginning of the study and after 36 days of treatment with 250 mg twice daily. For unchanged ticlopidine there were no significant differences between the concentration profiles for the two study groups. By day 36 the minimum concentrations in plasma were identical (0.35 +/- 0.22 mg/L and 0.36 +/- 0.21 mg/L, respectively). Using 14C-labeled ticlopidine, the concentration profiles of radioactivity on day 1 were similar to those on day 36 for both groups. However, maximum concentrations and area under the concentration-time curve at 72 hours were both higher in patients with renal failure than in healthy volunteers. Treatment with ticlopidine progressively decreased sensitivity to adenosine diphosphate-induced platelet aggregation. At day 36, the concentration of adenosine diphosphate required to achieve 50% platelet aggregation was approximately 2.5 times greater than before treatment. Both patients and healthy volunteers exhibited closely comparable changes. The response to collagen-induced platelet aggregation was not changed in patients by treatment with ticlopidine. In contrast, volunteers required a three- to fourfold increase in collagen concentration to achieve 50% platelet aggregation after 36 days of therapy. Although some differences in both pharmacokinetics and pharmacodynamics of ticlopidine have been demonstrated between patients and and healthy volunteers, results in this study demonstrated that a change of dosage is not required in renal failure.

Blood Platelet Reactivity and its Pharmacological Modulation in (People with) Diabetes Mellitus

“…Maximal inhibition is achieved in 4-7 days, and apparently lasts for 7-10 days, until 'fresh' platelets enter the circulation [223,223,224,288,289]. Both Ticlopidine and Clopidogrel act synergistically with other antiplatelet agents, like aspirin or GPIIb-IIIa antagonists, as they target different platelet activation pathways [290,291].…”

Effects of Ticlopidine on the Pharmacokinetics of Diltiazem and Its Main Metabolite, Desacetyldiltiazem, in Rats

“…It has been tried in a variety of platelet-dependent disease states (Gent et al, 1989;Hass et al, 1989;Janzon et al, 1990). Indeed, several recent reviews recommend ticlopidine as a valuable alternative when patients cannot tolerate aspirin (Haynes et al, 1998;Verhaeghe, 1991;Ito et al, 1992;Solomon and Hart, 1994;Buur et al, 1997;Ko et al, 2000).…”

Pharmacokinetic Drug Interaction between Carvedilol and Ticlopidine in Rats

“…It has been tried in a variety of platelet-dependent disease states (Gent et al, 1989;Hass et al, 1989;Janzon et al, 1990). Indeed, several recent reviews recommend ticlopidine as a valuable alternative when patients cannot tolerate aspirin (Verhaeghe, 1991;Ito et al, 1992;Solomon and Hart, 1994;Buur et al, 1997;Haynes et al, 1998;Ko et al, 2000).…”