Mammoth
Preclinical Consulting
Mammoth
Preclinical Consulting
Pharmaceutical Discovery & Development Consultants
Our Services
PRECLINICAL STUDIES
In vivo Pharmacokinetics, Xenobiotic Disposition and Metabolism
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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.
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Pharmacokinetic, toxicokinetic PK/PD Modeling applications in:
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Certara WinNonlin (user since 1991)
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Physiologically Based Pharmacokinetic Modeling (PBPK) cross species translation in multiple platforms:
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PK-Sim
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Berkeley Madonna
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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)
Physiologically Based Pharmacokinetic Modeling (PBPK)
Analysis Plans
Study and Dosing Simulations
Comprehensive Submission-Ready Packages for Regulatory Authorities
Design and Interpreting Nonclinical and Clinical ADME Studies
Characterize drug exposure
Determine an appropriate dose for a clinical study
Assess changes in dose requirements
Estimate the rate of elimination and absorption
Assess relative bioavailability/bioequivalence
Understand concentration-effect relationships
Establish safety margins and efficacy characteristics
IN VITRO ADME/PK
In vitro metabolism and enzyme kinetics
Stability in subcellular fractions
Hepatic CYP Inhibition
Plasma and tissue protein binding
In vitro metabolite identification for tox species selection
DEVELOPMENT SUPPORT
Regulatory document preparation
Study placement and monitoring
Sandra Dunn, PhD
CEO & Founder,
Phoenix Molecular Designs
“I have known Ed for over two decades and he continues to impress me. His preclinical toxicology experience is extensive and spans multiple disease verticals making him an extremely talented leader who has a proven track record in building numerous successful IND submissions to the USA FDA as we as International regulatory bodies in Europe and Asia. “
Kosalaram Goteti
Senior Scientific Director & Portfolio Section Head, Quantitative Pharmacology Merck Group
"I really enjoy working with Ed. He is scientifically sound in his M&S, PK/PD skills. In addition, He has broad experience in toxicology, ADME and pharmacology. …He guided our group to scientific excellence both internally and externally by publications, posters and presentations. He is one of those persons who gives his heart for the company, his people and the department working 24/7."
Enrique Alvarez Sotomayor, DVM, MA
Co-Founder, Sr. VP R&D
Pangolin Therapeutics
“Mammoth Preclinical Consulting offers critical and timely support in PK/PD modeling for the biotechnology sector. Mammoth uses a holistic approach that allows for the advancement of new drug candidates, with the work always focusing on the many aspects required to select a proper dose for clinical development. Ed uses his deep understanding of chemistry, biology, math and pharmacokinetics to help clients make their best decisions.”