PHARMACOKINETICS AND EFFECT OF TICLOPIDINE ON PLATELET-AGGREGATION INSUBJECTS WITH NORMAL AND IMPAIRED RENAL-FUNCTION

The pharmacokinetics and the effect of ticlopidine on platelet aggrega tion were determined in patients with chronic renal failure (n = 6), w ho were not on dialysis and had glomerular filtration of 16.9 +/- 4.4 mL/min, and were matched with the pharmacokinetics and effects in heal thy volunteers (n = 7). Participants were studied after acute oral adm inistration of ticlopidine at the beginning of the study and after 36 days of treatment with 250 mg twice daily. For unchanged ticlopidine t here were no significant differences between the concentration profile s for the two study groups. By day 36 the minimum concentrations in pl asma were identical (0.35 +/- 0.22 mg/L and 0.36 +/- 0.21 mg/L, respec tively). 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-tim e curve at 72 hours were both higher in patients with renal failure th an in healthy volunteers. Treatment with ticlopidine progressively dec reased sensitivity to adenosine diphosphate-induced platelet aggregati on. At day 36, the concentration of adenosine diphosphate required to achieve 50% platelet aggregation was approximately 2.5 times greater t han before treatment. Both patients and healthy volunteers exhibited c losely comparable changes. The response to collagen-induced platelet a ggregation was not changed in patients by treatment with ticlopidine. In contrast, volunteers required a three- to fourfold increase in coll agen concentration to achieve 50% platelet aggregation after 36 days o f therapy. Although some differences in both pharmacokinetics and phar macodynamics of ticlopidine have been demonstrated between patients an d and healthy volunteers, results in this study demonstrated that a ch ange of dosage is not required in renal failure.