The H3D Drug Metabolism and Pharmacokinetics (DMPK) team routinely conducts in vivo PK (pharmacokinetics) evaluation studies and our platform capabilities are highlighted below.
DMPK studies are important for estimating the basic PK parameters of a compound and associated optimization of compounds for human use or consumption. See the table below for additional details, including average turnaround time and control(s). For assays where an average turnaround time/control(s) are not available, this indicates that turnaround time is dependent on your unique experimental design and conditions; please book a consultation for an estimated turnaround time or additional information.
H3D's expertise and experience is especially pronounced in the following DMPK areas:
- Physiologic based pharmacokinetic modeling (PBPK)
PBPK is a computer modeling approach that uses mathematical equations to incorporate the effects of blood flow and tissue composition of organs into PK simulations for a compound and can be used to predict the PK properties of a drug inside the body.
- IVIVe (in vitro to in vivo extrapolation)
Physiologic and metabolic data gathered from PBPK modeling is coupled with IVIVe to quantitatively bridge in vitro and in vivo data in order to explore and clarify the key mechanisms dictating a compound's pharmacokinetics (PK). Can be used to predict clearance.
- Allometry for human PK
Allometry is the study of biological scaling, or how processes such as metabolic rates vary according to body mass; and allometric scaling is used to predict human PK based on animal data before any human clinical studies are conducted.
- Dose prediction
Quantitative dose prediction is key for estimating systemic exposure in human clinical studies.
Data from these assays can be used for lead optimization and drug candidate evaluation and results from these assays thereby inform key decision making and experimental design of human and/or animal in vivo studies.
See below for explanations of our capabilities.
- Dried Blood Spot (DBS) PK
Dried blood spot or dried blood sampling (DBS) is an innovative sampling technique where whole blood samples are blotted on an absorbent filter paper for experimental and diagnostic purposes; in comparison with the conventional “standard” venous blood collection, which does not allow for convenient, easy transportation to analytical labs. This is especially relevant for translational studies focused on rural, high temperature, and/or low-income settings.
- IV and PO (oral) PK in mice and rats
IV and PO (oral) dosing studies are performed in mice and rats to determine pre-clinical PK parameters and bioavailability. This data is combined and expanded upon using the studies outlined below as well as additional studies described on H3D's platforms and services pages. The best studies for you depend on your ultimate drug discovery and development goals.
- Dose Fractionation Studies
Dose fractionation studies are used to evaluate the differences in dose relative to a compound's efficacy and toxicity, and are key to eventual determination of the drug dosing regimen of a given drug candidate. This is because only a certain fraction of each dose for any given drug is actually absorbed and able to become pharmacologically active. It is very important to carefully evaluate these parameters before moving onto experimental design of human clinical trials.
- Metabolic Cage (Met ID, metabolism, excretion) Studies
Metabolic cage studies provide accurate measurements and detailed analysis of holistic metabolism information. These studies allow for collection and separation of different excretions and outputs Metabolic cage studies provide accurate measurements and detailed analysis of holistic metabolism information. These studies allow for collection and separation of different excretions (urine, feces, exhaled air or carbon dioxide) and outputs during a defined window of time.
- PK/PD (pharmacokinetic/pharmacodynamic) relationships
The purpose of PK/PD modeling studies is to link pharmacokinetics (dose-concentration, or the movement of drugs through the body over time) and pharmacodynamics (dose-effect, or the body's biological response to drugs) data in order to evaluate, quantify, and establish meaningful relationships between these parameters. This approach is an alternative to conventional dose-effect analysis, and here drug effects are related to drug concentrations (in a specific body compartment) rather than a drug dose.
- Human Dose Predictions
Human dose prediction is an important part of drug discovery and relies on the data and parameters collected during all previous phases of drug discovery. Quantitative estimation of human doses for early (Phase I) clinical trails is key for estimating systemic exposures and advancing a drug candidate further along in the development process, as well as informing the ranking of leads and lead optimization for human clinical trials.
| Assay Group | Assay Specifications |
|---|---|
| in vivo Pharmacokinetic (PK) studies | |
| in vivo PK study | Dried Blood Spot (DBS) PK |
| in vivo PK study | mouse (PO or IP) |
| in vivo PK study | mouse IV |
| in vivo PK study | mouse full PK (48 hour) |
| in vivo PK study | mouse full PK (24 hour) |
| in vivo PK study | rat full PK |
| in vivo PK study | mouse tolerability |
| in vivo PK study | mouse dose escalation (3 doses) |
| Metabolite Identification (Met ID) studies | |
| Metabolite Identification (Excretion) | excretion study + full Met ID |
| Metabolite Identification | targeted in vivo Met ID using PK samples |
| Metabolite Identification + in vivo PK study | full in vivo Met ID (using PK samples) |