Abstract
The phase one study was performed by the use of the single and multiple intravenous administration of newly developed synthetic antithrombin agent: (2 R, 4 R)-4-methyl-l- [N2- [(3-methyl-1, 2, 3, 4-tetrahydro-8-quinolinesulfonyl)-Larginyl] -2-piperidinecarboxylic acid monohydrate; MD-805]
As a single administration study, each one of groups consisting of six healthy volunteers was injected with one of 2.25mg, 4.5mg and 9mg of this agent by drip intravenous infusion taking 30 minutes and as a multiple administration study, 5 volunteers were injected with 9mg of the agent intravenously in three hours once a day for three days.
The clinicopharmacological reactions of this agent were evaluated with many parameter tests and clinical manifestations.
The evaluation from clinical symptom after the administration of this agent revealed no abnormality without spontaneous bleeding. However, the prolonga-tion of thrombin time, PTT and prothrombin time and the defect of platelet aggregation induced by thrombin were observed. These findings might be caused by main pharmacological action of this antithrombin agent.
On the other parameter tests, serum LDH level was slightly decreased on the cases of both single and multiple administration of this agent and A/G ratio was increased within normal range on single administration with this agent. All others of the safety parameters were within permitable changes in the clinical point of view.
On the basis of these results, we concluded that this agent can be applicable for phase two study.
