Mass balance and metabolite profiling of ¹⁴ C-Zalunfiban in humans following single-dose subcutaneous administration

The human metabolic and excretion profile of zalunfiban, a novel glycoprotein IIb/IIIa inhibitor, was studied in a phase 1 clinical trial.¹⁴C-zalunfiban was administered subcutaneously as a single fixed dose (9.5 mg with 5 μCi total radioactivity).Zalunfiban whole blood concentrations were measured using liquid chromatography-mass spectrometry. ¹⁴C-zalunfiban and metabolites were measured using liquid scintillation counting and accelerator mass spectrometry in whole blood, urine, and faeces. Eight participants were enrolled. Zalunfiban was well-tolerated.Following injection zalunfiban was detectable within 5 minutes and the last measurable concentration was observed within 4 hours. The median T_max was 0.25 hours and mean half-life was 0.96 hours. Zalunfiban accounted for 35.6% of total whole blood radioactivity AUC at 4 hours. The single major identified metabolite was des-gly-zalunfiban (M1), which has <1% of zalunfiban's antiplatelet activity. M1 was the primary urinary metabolite (52.98% of dose) with minor amounts of zalunfiban (1.31%) detected. M1 was also the major metabolite in faeces (2.87%). Total dose recovery reached >90% by 240 hours.Zalunfiban is rapidly metabolised to the nearly inactive M1 metabolite, which is excreted primarily in urine. Renal impairment, therefore, is unlikely to significantly prolong zalunfiban effects and dose adjustment in patients with reduced renal function may not be required.