PK & Safety
Pharmacokinetics (PK) studies provide the basis for interpreting the dose-related efficacy, safety and toxicological effects of a New Chemical Entity. InterVivo's advanced surgical techniques and depth of PK expertise provides a unique combination of quality, reliability and value for sponsors throughout the drug development process.
Through the PK-Bridge program, InterVivo supports early screening paradigms designed to identify and select NCEs with favourable PK properties. In addition, by customizing study designs, using advanced dosing and sampling techniques, and combining PK with efficacy and safety endpoints, InterVivo helps further characterize leads to aid the transition to successful clinical trials.
We offer a multi-species capability for early safety assessment, with primary focus on CNS function. Exploratory drug safety studies function to identify potential safety concerns about an NCE prior to formal transition into the development phase. Although these studies are not formally conducted to GLP, they are conducted and reported to a level compatible with regulatory requirements for IND (or equivalent) submission. This service provides the following advantages.
- Firstly, to discover risks of an NCE at the earliest stage to enable informed financial and technical resource decisions. Front-loading safety studies into the discovery phase is recognized as a valuable practice within the Pharma/Biotech community today (Lindgren et al, 2008).
- The data can be used to help define dose regimens for subsequent GLP toxicology studies.
- The results help establish side effect profiles of an NCE, that can be compared with competitor compound to facilitate product differentiation.
We offer multiple options in rodents, many of which can be extended to the Beagle dog, providing a seamless transition of safety testing to a higher species.
A Functional observation test battery for either the rat or mouse adapted from the Irwin (1968) test screen, and incorporating additional objective measures of motor and autonomic function.
Animals can be chronically treated with an NCE under staggered designs such that 2nd/3rd level dosing can be determined by the effect at first dose. Daily observation, blood chemistry and cell counts are included. Additional options include: major organ histopathology; plasma sampling for toxicokinetic profiling; CSF sampling (in the dog); and incorporation of a functional CNS test battery into the study design. Our emphasis is on flexible designs to maximize the value of information to the customer to guide subsequent efficacy and GLP toxicology studies.
Frequently, drugs are administered in combination with another therapy. We offer the capability to test for potentially deleterious drug-drug interactions, both at the behavioural and pharmacokinetic level.
Animals can be treated with an NCE by either iv, sc, ip or oral routes of administration and plasma samples taken at multiple timepoints. Additional tissue samples, e.g. csf (rat) can be taken to determine CNS penetration of NCE. These can also be coordinated with efficacy studies to support PK-PD determinations.
Unique adverse effects may be suspected based on the pharmacological property or observations made during the drug characterization process. Additional concerns may arise during clinical trials. In such cases, follow-up studies are recommended (ICH S7A). We can provide the following supplemental services:
- Tests for dependence and abuse liability;
- Tests for cognitive liability; and
- Tests for pro-convulsant liability.