5602

B201 (NSC-710295) is a demeric bradykinin antagonist. It has also been shown to be a biased antagonist for peptide receptor-G protein interactions and potently inhibits cell proliferation and stimulates apoptosis. B201 has shown promise as a cancer therapeutic. Previous studies indicated that intravenous and subcutaneous infusions of B201 caused hypotension and heart rate increases. The objective of this study was to determine whether the trifluoroacetic acid (TFA) component of the B201 (NSC-710295) formulation was responsible for blood pressure decreases and heart rate increases noted in previous evaluations of B201. Doses of 0 mg/kg (vehicle) and TFA in saline equivalent to 5 mg/kg of B201 were administered (intravenous). Four monkeys, 2 male/2 female, were used in a crossover design, resulting in data from four animals in both the vehicle and test article groups. Clinical observations, body weights, and cardiovascular data (systemic arterial blood pressures, heart rate, ECG waveforms, and ECG interval measurements) were all evaluated. There were no vehicle-related changes in blood pressures, heart rates, ECG’s, clinical observations or body weights following intravenous administration of pH unadjusted 5 mg/kg B201 equivalent. Due to the lack of cardiovascular response to the pH unadjusted formulation, it was concluded that the cardiovascular alterations observed following administration of B201 in previous studies cannot be attributed to the TFA component of the formulation. [Supported by N01-CM-42200]

98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA

American Association for Cancer Research
2007