Zaynich: genotox, carcinogenicity and repro: done or skipped?

“Zidebactam was negative for genetic toxicity in vitro in a mutagenicity assay in mouse lymphoma cells, and a chromosomal aberration assay in human peripheral blood lymphocytes, and in vivo in a mouse micronucleus assay in bone marrow cells.”

“Long-term carcinogenicity studies have not been performed with cefepime or zidebactam.”

“In pregnant rabbits, intravenous administration of zidebactam during organogenesis was associated with increased late fetal resorptions and total fetal loss in two litters at a dose of 600 mg/kg/day (approximately 5 times the RHD) and distended bladder, a fetal anomaly, at zidebactam doses greater than or equal to 300 mg/kg/day (approximately 3 times the RHD).”

“None of the infusions of 300 mg/kg WCK 5107 (zidebactam), 300 mg/kg cefepime, or the combination doses of cefepime plus WCK 5107 (300 mg/kg cefepime + 300 mg/kg WCK 5107 and 300 mg/kg cefepime + 150 mg/kg WCK 5107) induced changes in heart rate or arterial blood pressure or changes in any of the cardiac intervals compared to the control group in conscious male and female Beagle dogs.”

“WCK 5107 was not mutagenic in the test assay conditions with and without metabolic activation in concentrations of 0.015 mg/ml for TA98, 0.05 mg/ml for TA100, 0.015 mg/ml for TA1535, and 14.9 mg/ml for the TA1537 and WP2 uvrA strains.”

“Zidebactam was negative for genetic toxicity in vitro in a mutagenicity assay in mouse lymphoma cells, and a chromosomal aberration assay in human peripheral blood lymphocytes, and in vivo in a mouse micronucleus assay in bone marrow cells.”

“Zidebactam was negative for genetic toxicity in vitro in a mutagenicity assay in mouse lymphoma cells, and a chromosomal aberration assay in human peripheral blood lymphocytes, and in vivo in a mouse micronucleus assay in bone marrow cells.”

“Long-term carcinogenicity studies have not been performed with cefepime or zidebactam.”

“Long-term carcinogenicity studies have not been performed with cefepime or zidebactam.”

“However, none of the tested concentrations of WCK 5107 including the high concentration of 1461 mcM produced greater than 10% channel inhibition. Consequently, the IC50 value could only be estimated to be > 1461 mcM WCK 5107.”