Physiochemical properties, safety and pharmacokinetics of bimosiamose disodium after intravenous administration.
OBJECTIVE
Bimosiamose is a novel synthetic panselectin antagonist being developed for the treatment of acute and chronic inflammatory disorders. Therefore, we have studied the pharmacokinetics and tolerability and determined the pharmacokinetically relevant physicochemical characteristics of bimosiamose.


METHODS
A randomized, double-blind, placebo-controlled dose-escalation trial in healthy male subjects has been carried out. The subjects received intravenous infusions of 0.5-30 mg/kg bimosiamose disodium.


CONCLUSIONS
The maximum plasma concentration (Cmax) was 675 +/- 11 microg/ml with a tmax of 0.36 +/- 0.13 h (mean +/- SD). The elimination half-life t1/2 was 4.1 +/- 1.0 h, and the AUC(o-inf) was 1,360 +/- 393 h microg/ml after the 30 mg/kg dose. The clearance and the apparent volume of distribution decreased with increasing dose to 22 +/- 6 ml/kg/h and 40 +/- 13 ml/kg/h at the highest dose, respectively, and the mean residence time increased to 1.8 +/- 0.35 h. Bimosiamose was safe and well-tolerated.
Meyer
M
M
Revotar Biopharmaceuticals AG, Hennigsdorf, Germany. m.meyer@revotar-ag.de
Jilma
B
B
Zahlten
R
R
Wolff
G
G
D000328:Adult; D019540:Area Under Curve; D003877:Dermatitis, Contact / Q000209:etiology; D004244:Dizziness / Q000139:chemically induced; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D006207:Half-Life; D006586:Hexanes / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007262:Infusions, Intravenous; D008297:Male; D008358:Mannose / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D008657:Metabolic Clearance Rate; D015394:Molecular Structure; D012995:Solubility
D006586:Hexanes; C496819:bimosiamose; D008358:Mannose