ADME/PK

Southern Research has more than 40 years of specialized experience executing comprehensive ADME/PK services in support of drug discovery and development programs. Our diverse client list includes pharmaceutical, biotechnology, government and academic partners. In state-of-the art, GLP-compliant facilities, our highly trained professionals provide clients with critical data required in the preclinical assessment phase in pursuit of IND applications and NDA approvals. In addition, we offer the ability to provide customized study designs to meet our clients' specific needs. These studies may be conducted using radiolabeled or nonradiolabeled test articles.

Test Species

• Rodents, including rats, cotton rats, nude and transgenic mice, and tumor-bearing mice and rats
• Dogs
• Nonhuman primates
• Rabbits
• Ferrets
• Mini-pigs

Routes of Administration

• Oral (gavage or capsule)
• Parenteral
• intravenous
• subcutaneous
• intradermal
• intramuscular
• intraperitoneal
• dermal
• rectal
• continuous infusion
• Surgical implant

Pharmacokinetics

Southern Research scientists have extensive experience in the design and execution of single and multiple-dose pharmacokinetic studies to analyze multiple parameters, including the examination of dose proportionality, bioavailability, and food effects. In addition, we offer clients the capability of conducting toxicokinetic assessments of systematic exposure in conjunction or simultaneously with ongoing toxicology studies. A range of analytical support is available for these studies including radioassay, LC-MS/MS, HPLC, CE and immunochemistry.

Experienced, qualified pharmacokineticists are available within Southern Research to assist clients with study design, pharmacokinetic modeling, statistical analysis, and data interpretation. These skilled professionals can perform pharmacokinetic (PK), toxicokinetic (TK), or pharmacodynamic (PD) analyses on bioanalytical data generated at Southern Research as well as client-submitted data sets from preclinical and clinical studies. WinNonlin^® software is utilized for these analyses.

Compartmental and non-compartmental methods are utilized to examine multiple parameters in defining the pharmacokinetic profiles of compounds. Southern Research utilizes the following standard pharmacokinetic parameters (additional parameters are available upon client request):

• Maximum concentration (C_max)
• Time of maximum concentration (T_max)
• Area under concentration time curve (AUC_0-∞ and AUC_last)
• Volume of distribution (V_d)
• Clearance (CL)
• Terminal elimination half-life (t_½)
• Bioavailability

Pharmacokinetic Services/Capabilities Include:

• Single and multiple dose evaluations varying by species and administration routes
• Absolute bioavailability to determine extent of absorption
• Relative bioavailability for comparison of formulation/administration route
• Dose proportionality and linearity of absorption and disposition kinetics
• Pharmacokinetic species-to-species extrapolations
• Toxicokinetic support for acute, subchronic, and chronic studies

Absorption, Distribution, Metabolism and Elimination

ADME Services/Capabilities Include:

• Protein binding determinations
• Mass balance
• Rates and routes of elimination
• Single and multiple dose tissue distribution evaluations, including isolation and identification of metabolites in plasma, serum, urine, feces, bile and special tissues (CSF, ocular)
• In vitro metabolic profiling
• Pathway definition and species-to-species comparisons