Pharmacokinetics of the anticoagulant ¹⁴C-DX-9065a in the healthy male volunteer after a single intravenous dose

Abstract

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 ¹⁴Clabelled 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 biexponential 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 clearancesuggested 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.