In vitro biocompatibility studies with the experimental anticancer agent BIBX1382BS

The novel anticancer agent BIBX1382BS is a representative of the human epid ermal growth factor receptor (EGFR) tyrosine kinase inhibitors. BIBX1382BS, for parenteral use, is formulated pharmaceutically as a lyophilized produc t containing 100 mg BIBX1382BS per dosage unit. This in vitro study was per formed to establish the optimal intravenous administration conditions (infu sion concentration and infusion rate) for the forthcoming clinical absolute oral bioavailability study of BIBX1382BS. BIBX1382BS infusion solutions ha ve a low pH in order to keep the substance in solution. We therefore decide d to investigate the hemolytic and precipitation potential of the drug in v itro. Also, the ratio of formulation (F) solution volume and a blood simula ns (B) volume necessary to reach the physiological pH, expressed as the FB- ratio, was determined in vitro. On the basis of the results obtained, it is advised to administer BIBX1382BS infusion at a concentration of 1 mg/ml an d a maximum infusion rate of 10 ml/min. This article describes the in vitro biocompatibility screening program. (C) 2000 Elsevier Science B.V. All rig hts reserved.