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Mammoth
Preclinical Consulting

Our Services

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PRECLINICAL STUDIES

In vivo Pharmacokinetics, Xenobiotic Disposition and Metabolism​

 

  • Elucidation of the fate of small molecules via design and conduct of single and repeat dose rodent, canine, and non-human primate pharmacokinetic, disposition and metabolism studies with radioisotopes, stable isotopes and un-labelled molecules.

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  • Extensive experience in oral, IV, dermal, ocular and pulmonary delivery in preclinical settings.

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  • Identification of metabolites via LC-MS/MS and NMR.

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  • Extensive capabilities in the use of in vitro methodologies for mechanistic investigation of biotransformation, pharmacology and toxicology.

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  • Transporter and metabolism studies using Caco-2, isolated perfused rat kidney, isolated perfused rat liver, Franz cell/Ussing chamber, and in situ perfused intestine models.

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  • Use of transgenic and chimeric animal models to investigate metabolic and toxicological endpoints.

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  • In vivo and in vitro Drug-Drug interaction studies.

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  • Whole Body Autoradiography (WBA) studies.

MODELING AND SIMULATION

Pharmacokinetic and Pharmacodynamic Modeling & Simulation


Using modeling and simulation from early discovery to Phase 1, we help you quantitatively understand the temporal relationship between the concentration of your drug and its  effect to de-risk your program, increase confidence in critical decisions, and help you reach your goals, smarter and faster. 


Pharmacokinetics vs. Pharmacodynamics


Pharmacokinetics (PK) is the movement of drugs through the body vs time, whereas pharmacodynamics is the body’s biological response to drugs vs time. In the simplest terms, pharmacokinetics is what the body does to the drug and pharmacodynamics is what the drug does to the body.


Pharmacokinetics integrates in mathematical expressions properties of the rates of a drug’s absorption, distribution, metabolism, and excretion (known as ADME).

Pharmacodynamics describes mathematically the rates by which biological processes in the body respond to changes in drug concentration. PK modeling integrates the ADME properties  as a function of time.  Models of PK/PD describes the temporal relationship a drug’s concentration and the biological response. 


Quantitative understanding the exposure-response relationship (PK/PD) is key to the development and approval of every drug. 

 

  • Pharmacokinetic, toxicokinetic PK/PD Modeling applications in:

    • Certara WinNonlin (user since 1991)

 

  • Physiologically Based Pharmacokinetic Modeling (PBPK) cross species translation in multiple platforms: 

    • PK-Sim

    • Berkeley Madonna 

    • Sim-CYP 

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  • Pharmacokinetic/pharmacodynamic study design and interpretation. 

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  • Interspecies scaling of pharmacokinetics to select preclinical toxicology and clinical doses.

PHARMACOKINETICS AND PHARMACODYNAMICS SERVICES

Compartmental and Noncompartmental PK Analysis (NCA)

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Physiologically Based Pharmacokinetic Modeling (PBPK)

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Analysis Plans

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Study and Dosing Simulations

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Comprehensive Submission-Ready Packages for Regulatory Authorities

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Design and Interpreting Nonclinical and Clinical ADME Studies

 

Characterize drug exposure

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Determine an appropriate dose for a clinical study

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Assess changes in dose requirements

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Estimate the rate of elimination and absorption

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Assess relative bioavailability/bioequivalence

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Understand concentration-effect relationships

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Establish safety margins and efficacy characteristics

IN VITRO ADME/PK

In vitro metabolism and enzyme kinetics

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Stability in subcellular fractions

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Hepatic CYP Inhibition

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Plasma and tissue protein binding​

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In vitro metabolite identification for tox species selection

DEVELOPMENT SUPPORT

Regulatory document preparation​

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Study placement and monitoring

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