Knowledge of the fate (Absorption, Distribution, Metabolism, Elimination) of a test substance is necessary to predict its action on a test subject. With Attentive, you have at your disposal a wide range of in-vivo test systems as well as protocols and reporting infrastructure to ensure you receive quality data in a timely manner to select the best test substance and doses for your programs. Attentive Scientists bring the experience necessary to excel at executing these studies to assist you by performing in-vivo studies during the discovery and lead optimization phases of your research
High Throughput PK
A test substance/compound that is going to be used to treat a disease needs to be biologically active, absorbed, distributed, metabolized and excreted. In-vivo dose formulations that will be administered to a test system require testing. Attentive Science can execute the pharmacokinetic assessment of your compound/test substance to allow you to get a quick read on if you have a “druggable” product.
Long Term PK
During the early discovery phases of development, characterization of relatively longer half-life substances, be it a small molecule, biologic or an extended-release formulation, may be incomplete due to the extended absorption or elimination phases. It is critical to fully characterize any long-term pharmacokinetic profiles to fully understand how the test substance behaves In-vivo.
Comprehensive Dosing Routes
Standard and specialty dose routes are selected to mimic your intended clinical route of administration and alignment with your future clinical programs: PO (Oral); IV (Intravenous); SC (Subcutaneous); IM (Intramuscular); IP (Intraperitoneal Dermal); Intra-cerebral, Intra-thecal, Intra-articular etc.
Partner Workflow Streams
Scientific integrity, quality, cost-effectiveness and regulatory compliance are essential considerations when you are selecting an outsourcing partner. Attentive Science partners with carefully selected specialty organizations for any nonclinical functions such as histopathology that are not performed in-house. Being experts, we like to work with other expert organizations.
Upon administration of a test substance to a test system, the pharmacokinetic and toxicity profile can also be dependent on the varying formulation that was used during discovery. Attentive Science will take your compound/test substance and formulate it in several vehicles (based on the type of molecule and utilizing our collective experience), and will administer it directly into a test system, collect blood samples in a timely fashion to determine if the test substance is present or not, as well as provide pharmacokinetic data endpoints.
studies to evaluate the relationship between various doses of your drug molecule and adverse events require close collaboration between scientists with multiple levels of expertise from the development company and the contract research organization (CRO). Attentive’s processes ensure transparent communication, collaboration and dialogue that will keep up with your ever-changing needs for lead optimization, candidate selection as well as regulatory-enabling studies
We partner with our clients during the early phase of Discovery to assess exposure of your test substance/compounds within the body and get an idea of potential toxicity of the compound. The discovery toxicology studies are designed to assess any adverse effects that occur after a single or multiple administrations of the test substance.
Maximum Tolerated Dose
Typically, doses are increased in these study types to help identify correlating toxicity. The highest possible repeat dosage level can be identified during a 7 – 14 day study, which in turn is used to extrapolate dosage levels for your subsequent regulatory toxicological study. The Maximum Tolerated Dose (MTD) is the maximum dose that can be given over a specified study period that will not compromise the survival of the test system.
Dose Range Finding
The Attentive Science team routinely conducts preliminary in-vivo toxicity studies to determine appropriate doses for your single and multiple dose studies. We provide flexible study designs during these test substance tolerance assays, to help ascertain relevant multiples of the efficacious dose.
Prediction of acute effects on target organs subsequent to administration of your test substance is an essential data point. The data obtained helps guide your design and dose selection for subsequent sub-chronic and chronic studies. With Attentive, you have additional repertoire of in-vivo test systems to help you evaluate potential acute effects.
In order to provide a standardized electronic dataset for your nonclinical data which will fulfill regulatory electronic common technical document (eCTD) submission requirements, a SEND dataset is required. Use of SEND enhances data review, enables data warehousing, data analysis and data visualization in addition to having a set of controlled terminology for our industry. The FDA requires a SEND dataset for non-GLP studies if those studies are part of your submission, as well as for the customary GLP studies.
Safety Pharmacology studies are designed to detect the potential undesirable pharmacodynamic effects of new chemical entities on physiological functions in relation to exposure in the therapeutic range and above. In addition to you obtaining scientifically robust data, you have access to a vast network of experts at Attentive
Prior to phase I clinical trials, the effects of a therapeutic on the cardiovascular (CV) system, which is a vital organ system, should be evaluated and characterized. The Attentive Science safety pharmacologist combines his/her knowledge from Physiology, Pharmacology and Toxicology to evaluate effects on the electrocardiogram (ECG), with particular emphasis on ventricular depolarization and repolarization, as well as any potential effects on blood pressure (BP) and heart rate (HR).
Central Nervous System
Central Nervous System (CNS) studies are conducted in a controlled environment (e.g., limiting extraneous noise, excessive entering and exiting the room, etc.) with a limited number of test systems to allow the observer time to make a number of post dose observations during the day. The ICH S7A Safety Pharmacology (Studies for Human Pharmaceuticals) guidance document states that motor activity, behavioral changes, coordination, sensory/motor reflex responses and body temperature should be evaluated.
The ICH S7A Safety Pharmacology (Studies for Human Pharmaceuticals) guidance document states that the effects of the test substance on the respiratory system should be assessed appropriately. Respiratory rate and other measures of respiratory function (e.g., tidal volume or hemoglobin oxygen saturation) should be evaluated. Respiratory assessments focus on measures of pulmonary ventilation. Respiratory rate, tidal volume and/or a measure of arterial blood gases as the recommended ventilatory measurement parameters.