Tolerability, pharmacokinetics, and pharmacodynamics of DX-9065a, a new synthetic potent anticoagulant and specific factor Xa inhibitor, in healthy male volunteers.
OBJECTIVE
The aim of this study was to assess the tolerability, pharmacokinetic and pharmacodynamic properties of DX-9065a, a novel low-molecule specific factor Xa inhibitor in healthy male volunteers.


METHODS
DX-9065a was intravenously administered to healthy male Japanese volunteers at doses of 0.625 to 30 mg. The drug concentrations in plasma and urine were measured and pharmacokinetic parameters were calculated. Coagulation time and bleeding time were also measured.


RESULTS
No serious adverse event was observed during or after administration of DX-9065a. The pharmacokinetics of DX-9065a in human subjects after intravenous dosing was linear. The simulated plasma concentrations of DX-9065 were well in accordance with the observed values. Though prolongation of coagulation times was dependent on plasma concentration of DX-9065, bleeding time did not increase even at the highest plasma concentration of 1640 ng/mL.


CONCLUSIONS
DX-9065a had a good correlation between linear pharmacokinetics and pharmacodynamics after intravenous administration in humans.
Murayama
N
N
Global Medical Department, Daiichi Pharmaceutical Co, Ltd, and the Waseda Clinic and the School of Medicine, Keio University, Tokyo, Japan.
Tanaka
M
M
Kunitada
S
S
Yamada
H
H
Inoue
T
T
Terada
Y
Y
Fujita
M
M
Ikeda
Y
Y
D000328:Adult; D000704:Analysis of Variance; D000925:Anticoagulants / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000652:urine; D019540:Area Under Curve; D044466:Asian People; D001760:Bleeding Time; D004311:Double-Blind Method; D065427:Factor Xa Inhibitors; D006801:Humans; D007275:Injections, Intravenous; D007564:Japan; D016014:Linear Models; D008297:Male; D009281:Naphthalenes / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000652:urine; D011422:Propionates / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000652:urine; D012016:Reference Values
C086910:(2S)-2-(4-(((3S)-1-acetimidoyl-3-pyrrolidinyl)oxy)phenyl)-3-(7-amidino-2-naphtyl)propanoic acid; D000925:Anticoagulants; D065427:Factor Xa Inhibitors; D009281:Naphthalenes; D011422:Propionates