In Vivo Pharmacokinetics Services for Drug Discovery

Ricerca Biosciences, a partnered drug development organization, offers a full range of pharmacokinetic services to complement the company's in vitro lead optimization program. These in vivo experiments used in conjunction with preliminary toxicity testing and selected animal models can be used to further optimize your lead candidate.

The study designs described below are intended as a guide only and can be tailored to suit individual requirements.

Drug Discovery Support

Pharmacokinetic studies in mice, rats, or dogs can be used to prioritize drug leads and select the optimal compounds during analog synthesis. The study data coupled with our strong in vitro screening capabilities can predict toxicity, absorption, metabolism, and protein binding. Simply designed experiments can also give metabolite information and an estimate of elimination without the need for radiolabeled drug substances.

Pharmacokinetics Studies

The purpose of these studies is to provide information on systemic exposure of a drug and any metabolites. This data can be used to explain pharmacological or toxicological issues and can also aid in the design of toxicokinetic studies. Pharmacokinetic parameters, such as AUC, half-life, clearance and volume of distribution, are also determined.

Identification of Metabolites In Vitro

Metabolic clearance rate has a great impact on the material circulating in plasma. Incubation of a drug with microsomes or hepatocytes not only provides information on metabolic stability but also allows the identification of metabolites. This is generally a simpler task compared to identification in excreta, because metabolites are present at high concentrations and in a relatively clean matrix.

Pharmacokinetics and Excretion in Rats

A single oral or intravenous dose is administered to groups of three males (and females). Typically, 6-8 blood samples are taken during the first 24 hours after dosing. Concentrations of drug in plasma are measured using LC-UV or LC-MS(/MS) to define the plasma concentration-time curve. Using in vitro metabolism data, concentrations of major metabolites can also be estimated. Collecting excreta during the study period and analysis of these samples for parent and metabolites gives an estimate of elimination.