Unmodified rodent, canine and non-human primate models are routinely used to determine C_max, AUC, half-life, and oral bioavailability of test compounds via oral and intravenous dosing, and to predict human pharmacokinetic parameters such as clearance rate and volume of distribution. Excretion of test compounds and metabolites into bile and urine can be monitored. A metabolite ID study can aid the selection of species for pre-clinical toxicology studies.

In addition to the unmodified animal models, Absorption Systems also offers various surgically ported models to help with formulation assessment. These include rats, dogs and mini-pigs fitted with intestinal cannulas used to deliver dosing solutions or suspensions, as well as dogs fitted with duodenal fistulas for dosing solids, semi-solids, capsules and tablets directly into the duodenum. In each of these models, the animals are allowed to recover from surgery prior to being dosed with drugs. The animals are awake during studies. Cannulated animal models are used to identify and evaluate barriers to bioavailability, i.e., factors such as gastric instability, poor membrane permeability, site-dependent absorption, and hepatic first-pass extraction that contribute to low oral bioavailability. Through the use of these models, we can evaluate each of these factors separately. In addition, the concentration-dependence of saturable processes such as hepatic extraction and carrier-mediated influx or efflux can be examined. These models are described in Research Reports ASLP2 and ASLP7.

The beagle dog with an intraduodenal fistula is a model that is useful for comparing solid dose forms such as tablets and capsules, containing either immediate-release or extended-release formulations without interference from gastric events. The use of fistula is discussed in the ASLP6 Research Report.