Single and multiple dose pharmacokinetics of ticlopidine in young and elderly subjects

Abstract

The pharmacokinetics of orally administered ticlopidine hydrochloride, a novel inhibitor of platelet aggregation, were determined both after a single dose and after 21 days of twice daily dosing in 12 young (mean 28.6 years) and 13 elderly (mean 69.5 years) subjects. Concentrations of unchanged ticlopidine in plasma were measured by g.l.c. After a single 250 mg dose of ticlopidine, the mean area under the curve, AUC (0-12 h) was 1.11 micrograms ml-1 h in young subjects and 2.04 micrograms ml-1 h in old subjects (P = 0.002). Mean values of t1/2,z in young and elderly subjects were 7.9 h and 12.6 h, respectively (P = 0.01). Steady state plasma drug concentrations were attained after 14 days of dosing with ticlopidine. After the final dose on day 21, AUC values in elderly subjects were 2-3 times those in young subjects (P less than 0.001). The plasma t1/2,z averaged 4.0 days for young subjects and 3.8 days for elderly subjects (P = 0.7). The longer t1/2,z and higher AUC values after multiple dosing probably reflect an increase in bioavailability of ticlopidine after repeated dosing, saturation of metabolism or insufficient analytical sensitivity to characterize the terminal elimination phase after single dose.