Pharmacokinetics of the anticoagulant 14C-DX-9065a in the healthy male volunteer after a single intravenous dose.
1. The plasma pharmacokinetics, excretion and metabolism of DX-9065a were studied in the healthy male Caucasian volunteer after a single intravenous dose of 10 mg 14C-labelled DX-9065a. 2. At the end of a 1 h infusion, the mean plasma concentration of total radioactivity was 380 ng ml(-1) (equivalent to unchanged DX-9065). Thereafter, it decreased in a bi-exponential manner and was below the detection limit by 48 h after dosing. The half-life for the distribution phase was 6.93 h. 3. The total radioactivity recovered in urine and faeces by 336 h post-dose was 83.8% of the administered dose, with excretion ongoing at the end of the 14-day collection. The major route of excretion was via urine, accounting for a mean of 77.6% of the administered radioactivity. The urinary excretion profile was biphasic, consisting of rapid (0-24 h) and slow (24-336 h) phases. A large renal clearance suggested that renal tubular secretion might contribute to the excretion of DX-9065 via urine. 4. No metabolite peaks in the radio-HPLC chromatograms of urine samples were detected, indicating that biotransformation of DX-9065 does not play a significant role in the elimination of DX-9065 in man.
Murayama
N
N
Drug Metabolism and Analytical Chemistry Research Laboratory, Daiichi Pharmaceutical Co., Ltd, Tokyo, Japan. muraycjs@daiichipharm.co.jp
McMahon
H
H
Young
C G
CG
McCracken
N W
NW
Okamura
Y
Y
Hakusui
H
H
Tanaka
M
M
D000328:Adult; D000818:Animals; D000925:Anticoagulants / Q000097:blood / Q000493:pharmacokinetics / Q000652:urine; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid; D005243:Feces; D000882:Haplorhini; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D009281:Naphthalenes / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D011422:Propionates / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D051381:Rats; D013997:Time Factors
C086910:(2S)-2-(4-(((3S)-1-acetimidoyl-3-pyrrolidinyl)oxy)phenyl)-3-(7-amidino-2-naphtyl)propanoic acid; D000925:Anticoagulants; D002250:Carbon Radioisotopes; D009281:Naphthalenes; D011422:Propionates