DMPK Services
In Vitro ADME and DMPK for Faster Drug Development
Drug Metabolism and Pharmacokinetics defines how a drug is absorbed into systemic circulation, distributed across tissues, metabolized by biological enzymes, and ultimately eliminated from the body. Collectively, these processes determine the onset, intensity, and duration of pharmacological action.
At PI Health Sciences, DMPK provides a scientific framework to understand and predict in vivo drug behavior by evaluating absorption characteristics, tissue distribution patterns, metabolic transformation, and excretion pathways. This integrated understanding is essential for optimizing exposure, ensuring safety, and enabling informed progression of drug candidates across discovery and preclinical development.
DMPK studies generate critical data to predict human pharmacokinetics, enabling informed dose selection and safety assessment. By systematically evaluating metabolic and transporter-mediated processes, DMPK also supports the assessment of potential drug-drug interactions, helping to minimize adverse effects and improve medication safety. In addition, DMPK data plays a central role in supporting regulatory submissions by demonstrating drug safety and pharmacokinetic rationale to regulatory authorities. When applied early and strategically, DMPK studies reduce overall development risk by enabling early identification and prioritization of optimal drug candidates.
Our Services
In Vitro ADME
We identify metabolic liabilities before they become expensive failures. Our high-throughput ADME suite provides the rapid feedback needed for effective SAR (Structure-Activity Relationship) modeling.
- Physicochemical Properties: Solubility (Aqueous solubility), LogD, and pKa determination.
- Metabolic Stability: Microsomal and hepatocyte stability across species (human, rat, mouse, dog, and non-human primates) to predict in vivo clearance.
- Permeability & Transporters: Caco-2, MDR1-MDCK, and PAMPA assays, including P-gp and BCRP substrate/inhibition studies to predict oral absorption and blood–brain barrier (BBB) penetration.
- Drug-Drug Interaction (DDI): CYP450 inhibition (IC₅₀) and induction, along with Plasma Protein Binding (PPB) to determine the "free drug" fraction.
In Vitro ADME
Small Molecules
Most In Vitro ADME assays are designed primarily for small molecules and fall fully withinr this modality.
- Solubility and Permeability: Aqueous and Thermodynamic solubility, Caco‑2, PAMPA, MDR1-MDCK, bidirectional transport, blood‑to‑plasma ratio.
- Distribution and Binding: Plasma protein binding, microsomal/tissue binding, brain/plasma or tissue partitioning.
- Metabolism: Liver microsome and hepatocyte stability, CYP and UGT phenotyping, reactive metabolite screening, In Vitro metabolite identification.
- DDI and Transporter Risk: CYP reversible and time‑dependent inhibition, CYP induction, transporter inhibition and substrate assays (P‑gp, BCRP, OATP, OCT, OAT, MATE, BSEP, etc.).
- Excretion: In Vitro biliary excretion models (sandwich‑cultured hepatocytes) and related transport assays.
Peptides
Peptides typically require greater emphasis on stability and less reliance on classic CYP-driven metabolism.
Highly Relevant Assays
- Plasma protein binding (particularly for modified peptides).
- Plasma and microsomal stability, and hepatocyte stability.
- Blood‑to‑plasma ratio and tissue partitioning where tissue targeting is important.
Selective or Optional Assays
- Permeability assays (Caco‑2 or MDR1-MDCK) for orally intended peptides or to explore transporter roles.
- Limited CYP/UGT phenotyping and inhibition when data indicate enzyme‑mediated metabolism or DDIs.
- Selected transporter assays when using specific uptake pathways are involved (e.g., peptide transporters).
ADCs
For ADCs, many classic small-molecule ADME assays apply to the payload, while specialized assessments focus on the antibody-drug conjugate.
For the Small‑Molecule Payload
- Solubility and permeability (often limited when the payload is not intended to be dosed as a free drug), plasma protein binding.
- Microsome and hepatocyte stability, CYP/UGT phenotyping, DDI and transporter inhibition and substrate assays.
For the conjugate
- Plasma stability of the linker–drug conjugate (linker stability assessment)..
- Tissue partitioning, particularly tumor vs normal tissues (in vivo), supported by In Vitro binding or uptake as needed.
- Limited In Vitro metabolite identification focused on linker cleavage and payload release.
Biologics (mAbs, proteins)
For large biologics, classic small‑molecule ADME assays have limited applicability; focus is more on binding, catabolism, and target‑mediated disposition.
Commonly Used Assessments
- Plasma protein binding is generally inherent (via Fc or molecular structure) and is typically not profiled using small-molecule methods.
- In Vitro stability in plasma, serum, and relevant biological matrices to support half-life expectations.
- Selected cellular uptake and processing assays (e.g., target‑mediated internalization) rather than standard permeability models.
Rarely or Not Used
- Caco‑2/PAMPA/MDR1-MDCK permeability, microsomal stability, CYP/UGT phenotyping, classic CYP-or transport DDI panels, and reactive metabolite screening are generally not applicable.
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DMPK
Drug Metabolism and Pharmacokinetics (DMPK) data are critical for selecting the right candidates, de‑risking development, and meeting regulatory expectations. Our DMPK services help you understand how your molecules are absorbed, distributed, metabolized, and excreted, so you can move forward with confidence.
Drug Metabolism and Pharmacokinetics (DMPK) studies provide the foundation for understanding a drug candidate’s absorption, distribution, metabolism, and excretion (ADME). High-quality DMPK data are essential for candidate selection, risk mitigation, dose prediction, and regulatory submissions.
Our integrated DMPK platform supports programs from early discovery through IND-enabling studies, enabling informed decisions on compound optimization, safety margins, and clinical translation.
What We Offer
From early discovery screening to IND-enabling studies, our DMPK team supports both standalone assays and fully integrated ADME/PK programs.
- In Vitro ADME: Solubility, permeability (Caco‑2, PAMPA), plasma protein binding, metabolic stability, CYP inhibition/induction, transporter assays.
- In vivo pharmacokinetics: Single- and multiple-dose PK, IV/PO studies, bioavailability, tissue distribution, PK/PD support in relevant preclinical species.
- Metabolite Identification & Profiling: Metabolite detection, structural elucidation, and pathway analysis using LC-MS/MS and high-resolution mass spectrometry to support safety and drug–drug interaction
- Modeling & Simulation: Integration of in vitro and in vivo data using physiologically based pharmacokinetic (PBPK) and population PK (PopPK) modeling to support first-in-human dose projections and regimen optimization.
- Bioanalytical Support: Robust method development, qualification, and validation with sensitive LC-MS/MS platforms under appropriate regulatory quality frameworks.
Core In Vitro DMPK assays
These studies are typically expected before or around first‑in‑human dosing.
- Physicochemical properties: Aqueous solubility, stability, and sometimes lipophilicity to support formulation and exposure predictions.
- Permeability Assessment: Caco-2 or other permeability models to estimate intestinal absorption potential and efflux transporter involvement.
- Plasma Protein Binding & Blood Distribution: Determination of binding in human and preclinical species to interpret free drug exposure, pharmacological activity, and safety margins.
- Plasma Protein Binding & Blood Distribution: Determination of binding in human and preclinical species to interpret free drug exposure, pharmacological activity, and safety margins.
- Enzyme Phenotyping & DDI Risk Assessment: Evaluation of CYP inhibition, induction, and metabolic pathways, along with UGT and transporter interaction screens, to assess potential drug–drug interaction risks
High-level summary table
| DMPK area | Typical IND-relevant assays/studies |
|---|---|
| Physicochemical | Solubility, stability, lipophilicity, basic formulation-support tests |
| Absorption | Caco-2/permeability, oral vs IV PK and bioavailability |
| Distribution | Plasma protein binding, blood:plasma ratio, selective tissue distribution as needed |
| Metabolism | In Vitro stability (liver microsomes/hepatocytes), metabolite ID, enzyme phenotyping |
| Excretion | Radiolabeled mass balance, urine/feces bile recovery where warranted |
| DDI risk | CYP/UGT inhibition and induction, key transporter interaction screens |
| Toxicokinetics (TK) | Exposure in species used for repeat-dose tox (single and multiple dose) |
In Vivo Pharmacokinetics (PK)
Our in vivo DMPK studies characterize systemic exposure, clearance mechanisms, and tissue distribution, enabling translation from preclinical models to human dose prediction.
- Multi-Species PK Profiling: Comprehensive PK studies (IV, PO, SC, IP) conducted in rodent and non-rodent species to evaluate systemic exposure and pharmacokinetic parameters.
- Bioavailability and Clearance: Determination of key PK parameters including oral bioavailability (F%), clearance (CL), half-life (T½), and volume of distribution (Vss).
- Tissue Distribution Studies: Quantification of compound distribution across tissues, including specialized studies for CNS penetration (brain-to-plasma ratios) and tumor accumulation.
- Excretion & Mass Balance: Characterization of elimination pathways through biliary and urinary excretion profiling, including studies using radiolabeled compounds when required.
Core in Vivo PK / ADME Studies
These studies establish the relationship between exposure, toxicity, and dose selection for clinical development.
- Single-Dose PK in Toxicology Species: PK studies conducted at or near doses used in repeat-dose toxicity studies, typically in one rodent and one non-rodent species, to characterize systemic exposure and toxicokinetics (TK).
- Multiple-Dose PK / Toxicokinetics: Collection of TK samples during repeat-dose toxicity studies to relate systemic exposure to observed toxicological findings and to support safe starting dose selection for first-in-human trials.
- Bioavailability & Basic Disposition: Oral versus IV PK studies to estimate bioavailability and assess absorption characteristics; tissue distribution studies may be included depending on compound properties and therapeutic area.
- Mass Balance & Excretion Studies: Radiolabeled ADME or mass-balance studies performed to determine routes of elimination and the presence of major circulating metabolites, typically completed before or during early clinical phases.
Why Our DMPK Platform
Our DMPK team combines state-of-the-art bioanalytical instrumentation, experienced scientists, and integrated pharmacology support to accelerate drug development decisions.
Key strengths include:
- Integrated in vitro–in vivo translation
- Advanced LC-MS/MS and HRMS capabilities
- Expertise across small molecules and emerging modalities
- Flexible study designs tailored to discovery, lead optimization, and IND-enabling stages
- Seamless integration with toxicology, pharmacology, and bioanalytical teams
Integrated PK/PD Strategy
Rather than evaluating pharmacokinetics and pharmacology independently, we integrate PK data with biological endpoints to define a compound’s therapeutic window and optimal dosing strategy.
- PK/PD Correlation: Simultaneous assessment of drug concentrations and pharmacodynamic markers such as target engagement, biomarker modulation, or efficacy endpoints.
- Dose–Response Characterization: Identification of the minimum effective dose (MED) and exposure thresholds required for pharmacological activity.
- Human Dose Projection: Use of allometric scaling, PBPK modeling, and translational PK/PD approaches to support first-in-human dose selection and clinical study design.
Bioanalytical Excellence
Our bioanalytical laboratories utilize high-sensitivity LC-MS/MS platforms to deliver accurate and reproducible quantification of drug candidates and metabolites across diverse biological matrices.
- Rapid Discovery Bioanalysis: Fast turnaround support for early PK screening studies.
- Method Development & Validation: Development and validation of non-GLP and GLP-compliant analytical methods for plasma, tissue, bile, CSF, and other complex matrices.
- Small & Large Molecule Expertise: Support for traditional small molecules, as well as emerging modalities including PROTACs, peptides, and other targeted therapeutics.
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Capabilities
Advanced Metabolite Identification
PI Health Sciences uses advanced mass spectrometry to accurately identify and characterize drug metabolites formed during metabolism studies.
Metabolic Pathway Understanding
Metabolite characterization reveals critical metabolic pathways, helping identify liabilities and guide compound optimization.
Regulatory Compliance
Robust quantitation data aligns with regulatory expectations and supports submission-ready PK and metabolism packages.
LC-MS/MS Technology
LC-MS/MS provides highly sensitive and specific quantitation of drugs in complex biological samples across PK and metabolism studies.
HPLC Applications
HPLC enables precise separation and quantification of drug components, strengthening overall bioanalytical reliability.
Pharmacokinetic Support
Quantitative data clarifies ADME behavior, supporting confident pharmacokinetic interpretation and development planning.
Frequently asked questions
We’re here to help with any questions you have about our plans, supported features, and how our model works.
How do In vitro ADME studies support medicinal chemistry optimization?
In vitro ADME studies provide rapid feedback on physicochemical properties, metabolic stability, permeability, protein binding, and drug-drug interaction risk. These data directly support structure-activity relationship modeling, enabling medicinal chemists to optimize drug-likeness while balancing potency and safety.
Which in vitro ADME assays are typically performed before first-in-human studies?
Common IND-relevant in vitro ADME assays include solubility and stability assessments, permeability studies such as Caco-2 or PAMPA, plasma protein binding, liver microsome and hepatocyte stability, metabolite identification, and CYP inhibition or induction screens to assess drug-drug interaction risk.
How do in vivo pharmacokinetic studies inform dose selection?
In vivo pharmacokinetic studies characterize exposure following different routes of administration and across species. Parameters such as bioavailability, clearance, half-life, and volume of distribution are used to define dosing strategies, interpret efficacy and safety findings, and support human dose projections.
How are metabolite identification and profiling used in DMPK?
Metabolite identification and profiling characterize metabolic pathways and identify circulating or unique metabolites. This information supports safety assessment, interpretation of clearance mechanisms, evaluation of species relevance, and identification of potential metabolite-driven liabilities.
What role does tissue distribution play in DMPK decision-making?
Contact Us
Connect with PI Health Sciences to explore how our DMPK capabilities can support your development programs, from ADME characterization and exposure assessment to translational pharmacokinetics and safety-informed decision making.