Established Pharmacology and Toxicology Models

Disease Pharmacology is a core component of groundbreaking drug development and disease models provide a critical path to drug discovery success. These models provide invaluable study endpoints, guide research efforts, and drive decision making for innovative therapeutic interventions. Inotiv has established and provides access to a wide range of in vivo, preclinical early-stage research models combined with drug efficacy, pharmacology, and safety studies.

Our experienced team of scientists has the expertise to offer a wide range of study designs in pharmacology and toxicology within multiple therapeutic and disease indications including neuroscience, GI/IBD, inflammatory/immunology, cardio-renal, hepatic, pulmonary disease, and more. Our hands-on collaborative approach means that our scientists will work with you to learn your specific preclinical study requirements and assist you from initial study design to final reporting with dependable, reproducible results.

Cardiovascular Disease and Injury

Myocardial infarction
Hypertension-based cardia dysfunction, hypertrophy, and failure
Cardiac hypertrophy, cardiac pressure overload, and heart failure

Left Ventricular Function, Cardiac remodeling and Histological evaluation
Methods: Echocardiography (M-Mode, B-Mode & Doppler), Pressure/Volume, Invastive LV Hemodynamics (+/-dP/dT, Tau, LVEDP and LVESP)
Disease Models: Myocardial Infarction, ZSF1, SHHF, Dahl Salt Sensitive (DSS) (additional models available)

Diabetic Complications

Type 1 diabetes
Type 2 diabetes
Metabolism and diet

Glucose and Insulin Tolerance Tests (OGTT/IPGTT)
Fasting and fed blood glucose
Cholesterol, HDL, LDL, Apolipoproteins, HbA1C, Microalbumin, Creatinine, etc.
Adipose tissue and body weight
Disease Models: Type I and II diabetes – ob/ob, db/db, DIO and STZ mice; ZDF and STZ rats (additional models available)

Hepatic Disease and Injury

Hepatic fibrosis
Other hepatic conditions
Collagen/Hydroxyproline content
Serum ALT/AST/ALP
Portal Vein Pressure
Histological evaluation

Models: Carbon Tetrachloride (CCl4) and Bile Duct Ligation (BDL)

Inflammatory Bowel Disease (IBD)

Neuroscience

Osteoarthritis (OA)

Osteoarthritis (OA) Models

Pain

Pulmonary Disease and Injury

Pulmonary fibrosis
Pulmonary arterial hypertension
Acute lung injury
Airway hyper-responsiveness (AHR)/asthma
Right Ventricular Systolic Pressure/Pulmonary Arterial Pressure
Heart and Lung Weight
Myocardial, Pulmonary Artery and Lung Histology

Disease Models: Monocrotaline PAH

Renal Disease and Injury

Acute kidney injury and failure (AKI/ARG)
Nephrotoxicity
Chronic kidney disease and renal insufficiency
Autoimmune kidney injury
Diabetic nephropathy
Proteinuria, albuminuria, GFR, Creatinine Clearance, histological evaluation
Plasma/Urine Biomarkers of damage
Chronic blood pressure monitoring using radio telemetry

Disease Models:: 5/6 Nephrectomy, Renal Ischemia/Reperfusion, Dahl Salt Sensitive (DSS), Streptozotocin (STZ), ZSF1, Unilateral Urethral Obstruction (UUO), Puromycin Aminonucleoside (PAN), Uninephrectomized (additional models available)

Systemic Autoimmune Rheumatic Disease (SARD)

Scleroderma

Lupus

Rheumatoid arthritis

Monoarticular inflammation/arthritis

Other Inflammatory Conditions

Anemia
Psoriasis
Dermatitis
Delayed type hyper-sensitivity
Anaphylaxis
Peritonitis
Acute edema
Pancreatitis

Toxicologic

Non-GLP discovery toxicology
Regulated IND/CTA enabling

Cardiovascular Safety
- Cardiovascular Telemetry Platform – Continuous measurement of blood pressure, heart rate, ECG, respiration, temperature & activity in conscious, unrestrained animals for up to 6 months. Blood, urine, fecal and tissue sampling available.
- Infusion Pharmacology Platform – Continuous infusion of test compound and simultaneous blood pressure & heart rate analysis for up to 14 days. Clinical observations, blood, urine, fecal and tissue sampling
- Cardiac, Lipid and Metabolic Biomarkers – Markers of tissue and biochemical damage (e.g. CK, CRP, chol, trigs, glucose, HbA1c, etc.)
- Echocardiography – Left Ventricular Function & Dimensions
- Left Ventricular Function – +/-dP/dt, Tau, LVEDP and LVESP

Renal Safety
- Renal Function – Creatinine Clearance, GFR, proteinuria and electrolytes
- Kidney Histology – Glomerulosclerosis, tubular damage, fibrosis, etc.
- Renal Biomarker Panel – Analysis of FDA/EMA approved urinary biomarkers that are predictive of drug-induced renal toxicity and translatable to human nephrotoxicity

General Safety and Toxicology (non-GLP)
- Chronic Infusion Studies – Continuous infusion of test agent for up to 14 days. Clinical observations, blood, urine, fecal and tissue sampling
- Hematology – 23-parameter complete blood count plus 5-point WBC differential analysis on blood samples from in-life studies
- Clinical Chemistry – 180 analytes available including markers of liver, kidney, cardiac, pancreas and bone damage; as well as lipids, metabolic and inflammation
- Histopathology – Standard or tailored to your target tissue of interest

Gastrointestinal Safety and Function
- Intestinal Motility – Charcoal meal test
- Intestinal Secretion – Closed and Open loop models of fluid and electrolyte secretion as well as compound absorption