Clinical study of KBT-3022: Platelet aggregation effects and pharmacokinetics in elderly (>= 65 years of age) and nonelderly patients with chronic arterial occlusion

Background: KBT-3022 is a new antiplatelet agent whose main mechanism of ac tion is cyclooxygenase inhibition. Objective: This study was conducted to investigate the clinical efficacy an d safety of KBT-3022, as well as its antithrombocytic action and pharmacoki netics in elderly (greater than or equal to 65 years of age) and nonelderly patients. Methods: Patients with chronic arterial occlusive disease (arteriosclerosis obliterans or thromboangiitis obliterans) were divided into 2 groups: elde rly (greater than or equal to 65 years of age) and nonelderly. KBT-3022 5 m g once daily was administered orally for 6 weeks. Blood sampling was perfor med before administration, at weeks 2 and 6, and 7 days after completion of administration. Platelet aggregation was measured with 3 aggregation induc ers using the platelet-rich plasma transmission method: 3 concentrations of adenosine diphosphate (ADP) (2, 5, and 10 muM); collagen 2 mug/mL; and ara chidonic acid 2 mM. Plasma concentrations of the drug were measured at the same time points. Changes in platelet aggregation before and after administ ration of the study drug were compared using the paired t test. Results: A total of 21 patients were enrolled in this study (11 in the elde rly [greater than or equal to 65 years of age] group and 10 in the nonelder ly group). Nine patients in the elderly group and 10 in the nonelderly grou p were included in the analysis of inhibition of platelet aggregation. Drug plasma concentrations were analyzed in 8 patients in the elderly group and 9 in the nonelderly group. In both groups, KBT-3022 significantly (P < 0.0 5) inhibited arachidonic acid-induced platelet aggregation at week 2 compar ed with pretreatment. In the elderly group, KBT-3022 significantly inhibite d ADP 5 <mu>M- and 10 muM-induced platelet aggregation at week 2 (P < 0.01 and P < 0.05, respectively) compared with pretreatment. In the nonelderly g roup, KBT-3022 significantly inhibited all 3 levels of ADP-induced platelet aggregation at week 2 (2 and 5 muM, P < 0.01; 10 <mu>M, P < 0.05) compared with pretreatment. The study drug also significantly (P < 0.01) inhibited collagen-induced platelet; aggregation at week 6 compared with pretreatment . There was no significant difference between groups in degree of aggregati on induced by the 3 agents. No difference in plasma clearance rate was obse rved between the 2 groups. Recovery to 80% of preadministration values was observed 7 days after completion of administration in >80% of patients. No patient withdrew because of exacerbation of disease or adverse events. Conclusion: In the present study, KBT-3022 5 mg administered orally once da ily inhibited platelet aggregation. Platelet aggregation returned to normal in most patients 7 days after completion of administration, indicating tha t the effects of KBT-3022 are reversible. There was no difference in inhibi tion of platelet aggregation between elderly and nonelderly patients, and t he previously determined optimal dose of 5 mg once daily can thus be prescr ibed without regard to patient age.