Bimosiamose is a novel synthetic pan-selectin antagonist developed for the treatment of acute and chronic inflammatory disorders. Therefore the pharmacokinetics of Bimosiamose disodium were studied in healthy male volunteers after single and multiple subcutaneous injections. A randomized, double-blind, placebo-controlled dose escalation trial was carried out. The subjects received subcutaneous injections of placebo or 100, 200 or 300 mg Bimosiamose disodium into the abdomen. Plasma and urine concentrations of Bimosiamose were determined. The maximum plasma concentration was 2.17+/-0.70 microg/ml and the AUC(0-infinity) 11.1+/-2.9 h microg/ml after the highest dose on day 1 (mean+/-SD). For the apparent clearance CL/f 28.7+/-7.3 l/h and the terminal half life t(1/2) 3.7+/-0.6 h were calculated. The mean residence time MRT(infinity) of 5.5 to 6.3 h for s.c. injection exceeded that after i.v. infusion due to an extended absorption time. For multiple dosing, constant pre-dose concentrations of about 20 ng/ml may be reached after two subsequent doses of 200 or 300 mg Bimosiamose disodium once daily. Almost 15% of the administered drug was excreted unchanged in urine. Moreover, Bimosiamose was well tolerated.
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