In vitro biocompatibility studies with the experimental anticancer agent BIBX1382BS

• Published in: International journal of pharmaceutics Vol. 194; no. 2; pp. 261 - 267
• Main Authors: Nuijen, B., Bouma, M., Henrar, R.E.C., Brauns, U., Bette, P., Bult, A., Beijnen, J.H.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 25-01-2000; Elsevier
• Subjects: Antineoplastic agents; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - adverse effects; Antineoplastic Agents - pharmacokinetics; Antineoplastic Agents - pharmacology; BIBX1382BS; Biocompatibility; Biological and medical sciences; Chemical Precipitation; ErbB Receptors - antagonists & inhibitors; FB-ratio; General aspects; Hemolysis; Hemolysis - drug effects; Humans; Medical sciences; Organic Chemicals; Pharmacology. Drug treatments; Precipitation; Hemolysis; BIBX1382BS; FB-ratio; Biocompatibility; Precipitation; Antineoplastic agent; Intravenous administration; Enzyme; Transferases; Enzyme inhibitor; Bioavailability; In vitro; Epidermal growth factor; Dosage form; Protein-tyrosine kinase
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/S0378-5173(99)00389-0

The novel anticancer agent BIBX1382BS is a representative of the human epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors. BIBX1382BS, for parenteral use, is formulated pharmaceutically as a lyophilized product containing 100 mg BIBX1382BS per dosage unit. This in vitro study was performed to establish the optimal intravenous administration conditions (infusion concentration and infusion rate) for the forthcoming clinical absolute oral bioavailability study of BIBX1382BS. BIBX1382BS infusion solutions have a low pH in order to keep the substance in solution. We therefore decided to investigate the hemolytic and precipitation potential of the drug in vitro. Also, the ratio of formulation (
F) solution volume and a blood simulans (
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 and a maximum infusion rate of 10 ml/min. This article describes the in vitro biocompatibility screening program.