Lower susceptibility to histaminergic reactions in rodents using continuous infusion: advantages for safety assessment of parenteral peptide/protein drugs

摘要

Some peptides, proteins and macromolecules elicit histaminergic responses in vitro and in vivo. Rodent vascular infusion models with surgically implanted indwelling catheters are available for repeated and/or prolonged infusion. The rat is probably the most commonly used animal for preclinical continuous infusion. However, rats are particularly susceptible to histaminergic reactions. Similarly, repeat intravenous (iv) bolus administration of drugs that elicit histaminergic-type reactions pose a particular problem in rodents, as for infiltration of an irritant solution around the tail vein (peri-vascular) can potentially lead to necrosis and make further injections difficult or impossible. As more parental therapeutic peptides/ proteins are developed, a less histaminergic-reactive model would offer improved safety testing via continuous/repeated infusion.