Pharmacokinetics Prediction

We offer multiple options for predicting PK, according to the data you have available. Read more below or, if you are uncertain, feel free to use our service selector to learn more about the service most suitable for you.

Start your compound optimization strongly by using our virtual pharmacokinetic (PK) parameter prediction service. We provide predictions of key PK parameters in human and rat based solely on compound structure. Prioritize compound synthesis, ADME or PK screening based on the most favorable predicted PK.

Human and rat PK prediction from structural descriptors:

• Robust predictions, ideal for virtual screening or assay prioritization

• Predictions of clearance, half-life, steady-state volume of distribution, oral dose AUC and oral dose Cmax

• Send structures as SMILES or sdf.

• No specialized staff required

• No software licensing costs

• Predictions within one working day of receipt of valid structures

• Scales seamlessly from a single compound to thousands of compounds

Compound structures – as either SDF or SMILES file.

• Send your compound structures to us.
• We will validate the structures, perform the predictions and return the predicted PK parameter values to you.

Results are returned as a single file containing:

• Columns of predicted clearance, half-life, steady-state volume of distribution, dose-normalized oral AUC [ (µg.h/ml)/(mk/kg) ] and dose-normalized oral C_max [(µg/ml)/(mk/kg) ], for rat and human.

• One row for each compound with predictions of rat and human PK parameters.

Virtual prediction refers to the prediction of a property using a model that does not require any data in vitro or in vivo data as input. Predictions are made from properties calculated from the known structure of the compounds in question. Consequently, no compound has to be synthesized – predictions can be made from ‘virtual’ compounds.

Suitable PK in both humans and pre-clinical animals is a prerequisite for a successful drug. With our virtual PK prediction service you can identify compounds expected to have suitable PK both in human and in the rat, enabling prioritization of compounds for synthesis and screening, saving money on unnecessary synthesis.

Contact us, and one of our experts will provide you with alternative options.

Prediction of in vivo pharmacokinetics (PK) from in vitro ADME data adds value to those data and provides a firm basis for prioritizing compounds for progression accounting for their expected in vivo behavior. Cyprotex offers two services for the prediction of PK from ADME data. Follow the links below for details of each:

• PK parameter prediction: obtain predictions of key summary PK parameters (rat and human options available)
• PK profile prediction: obtain simulated plasma profiles for selected iv or po dose regimes, with data and plots exported in Microsoft Excel (human only)

Increase the value of your human or rat early ADME data by using our pharmacokinetic (PK) prediction service. We provide predictions of key PK parameters in human or rat based on compound structures and ADME data. Prioritize compound progression based on the most favorable predicted PK.

Use data generated by Cyprotex or provide your own.

Human or rat PK parameter prediction from ADME data and structural descriptors:

• Robust predictions, ideal for prioritizing assay selection and compound progression.

• Predictions of species-specific clearance, half-life, steady-state volume of distribution, oral dose AUC and oral dose C_max

• Send structures as SMILES or sdf.

• No specialized staff required

• No software licensing costs

• Predictions within one working day of receipt of valid ADME data, if using Cyprotex in vitro ADME package

• Scales seamlessly from a single compound to hundreds of compounds with no added delay.

• Intrinsic clearance measured in either human liver microsomes or human hepatocytes
• Fraction unbound in human plasma
• Compound structures – as either SDF or SMILES file

Choose whichever of the following options is most appropriate:

• Send compounds for screening through Cyprotex’s ADME assays (species-specific rat or human plasma protein binding, hepatocyte stability or microsomal stability); structures in SMILES or sdf file. Predictions will be returned within one working day of ADME data being finalized.

• Send pre-generated data along with compound structures. Predictions will be returned within five working days of receipt of the data and structure package.

Results are returned as a single file containing:

• Columns of predicted clearance, half-life, steady-state volume of distribution, dose-normalised oral AUC [ (µg.h/ml)/(mk/kg) ] and dose-normalised oral C_max [(µg/ml)/(mk/kg) ], for rat or human, depending on the species selected.

• One row for each compound with predictions of rat or human PK parameters, depending on the species selected.

Suitable PK in both humans and pre-clinical animals is a prerequisite for a successful drug. Our PK prediction service provides reliable predictions of PK parameters with rapid turn-around time. For PK predictions without the need to synthesize and assay compounds, use our Virtual PK Prediction service.

Molecular descriptors calculated from compound structure carry significant amounts of valuable information for predicting many PK properties, and usually result in better models than can be generated without them, even when using measured ADME.

Contact us, and one of our experts will provide you with alternative options.

Maximize the value of your human early ADME data by using our pharmacokinetic (PK) profile prediction service to identify efficacious dose regimes to support compound progression. We offer prediction of human plasma PK for intravenous and/or oral dose regimens (single- or repeat-dose)  based on ADME data, with or without test article structures.

The service is flexible to suit your operational requirements: 

• You can use data generated by Cyprotex or provide your own.
• You can use measured physicochemical properties, or provide test article structures for structural descriptor calculation. 

Human pharmacokinetic simulation from in vitro ADME data and, optionally, structural descriptors:

• Predict pharmacokinetics (PK) for oral (po), intravenous (iv) bolus, or infusion regimens
• Plasma concentration-time profiles and summary PK parameters provided for maximum utility
• No specialized staff required
• No software licensing costs
• Predictions within one working day of receipt of ADME data, if using Cyprotex in vitro ADME data package
• Scales seamlessly from a single compound to hundreds of compounds, with no added delay

• Intrinsic clearance measured in either human liver microsomes or human hepatocytes
• Fraction unbound in human plasma

Either

• Compound structure – as either SDF or SMILES file

Or

• logP, logD at pH 7.4 and pKa(s)
• Optional human blood to plasma ratio
• Optional dose regimen

Choose whichever of the following options is most appropriate for you:

Option 1: Cyprotex in vitro screening

• Send compounds for screening through Cyprotex’s ADME assays (human plasma protein binding; human hepatocyte stability or microsomal stability; optional human blood to plasma ratio)
• Choose whether to add in vitro screening for logP and logD  and pKa , or to send structures for test articles (SMILES or sdf file)

Predictions will be returned within one working day of in vitro data being finalized.

Option 2: Provide your own in vitro data

• Send us your pre-generated values for human plasma protein binding, human hepatocyte stability or hepatic microsomal stability and optional human blood to plasma ratio.
• Choose whether to send additional logP, logD and pKa values, or to send structures for test articles (SMILES or sdf file).

Predictions will be returned within five working days of receipt of the data and structure package.
 

Predictions are delivered in an Excel workbook containing the following worksheet tabs:

• A summary sheet containing summary PK parameters for all combinations of compound and dose regimen simulated
• A single sheet for each compound/dose combination, containing:
  • Plasma concentration-time profile data for 24 hours following administration of final dose
  • Linear plot of plasma concentration-time profile
  • Semi-logarithmic plot of plasma concentration-time profile

Predicted PK parameters and plasma profiles can be easily read into databases or modelling software for further manipulation. Plots can be immediately copied into presentations or documents, or formatted to suit specific presentation requirements.

PK profile prediction generates a more extensive set of outputs, including plasma concentration: time profiles in tables and presentation-ready plots than the PK parameter service, but is currently only available for human prediction.

The choice largely depends on your operational procedures, and therefore whether you expect to have logP, loD and pKa values at the time your hepatic clearance and protein binding data are available to use in prediction. If so, whether measured at Cyprotex or elsewhere, these can be used in PK profile prediction. If not, providing the structures enables us to calculate molecular descriptors (pKa, logP, logD and others), that are used in the PK model.

Take advantage of our extensive PK modelling experience to maximize the value of your ADME and pharmacokinetic (PK) data. We can predict plasma/blood and tissue PK profiles and parameters in human or pre-clinical species for a wide range of pre-clinical or clinical scenarios.

• Use pre-clinical PK and ADME data to predict human PK
• Rigorous model development process
• Off-the-shelf models and bespoke modelling service are available
• Model complex PK scenarios:
  • Prodrug/drug/metabolite PK
  • Interacting compounds
  • Vascular and extravascular PK
  • Loading and maintenance doses
  • Model alternative administration regimens (oral, intravenous bolus, intravenous infusion, sub-cutaneous, intramuscular, etc.)
• Expert result interpretation, reporting and advice

• Plasma, blood or tissue concentration data from three or more pre-clinical species, and in vitro ADME data for the corresponding species
• Corresponding in vitro ADME data for human
• Compound structure – as either SDF or SMILES file

The process is an interactive one between the client and experts in Cyprotex’s Modelling and Simulation Group. Projects typically start with an assessment of the client’s in vitro and in vivo data, followed by discussion of the most appropriate modelling approaches that can be taken. Model development and assessment is conducted with progress updates and discussion with the client. The interval and nature of the feedback process is at the discretion of the client, as is the final reporting format.

Details of the results to be returned are usually specified before the start of each project, and will typically include:

• Assessment of the data provided by the client
• Details of model development process undertaken
• Details, including parameter values, of any models used or produced during the projects
• Results of modelling inter-species scaling, and extrapolations to human or other species
• Comparison of models, wherever more than one model is involved
• Predictions of human plasma/blood/tissue PK for one or more dosing regimens to be selected by the client.

The nature of the deliverables to be generated are usually specified before the start of each project, and will typically comprise one or more of the following:

• Presentations with slide sets typically in Microsoft PowerPoint.
• Prose reports, typically in Microsoft Word.
• Files (e.g. csv or Microsoft Excel) containing predicted plasma/blood/tissue concentrations and/or calculated PK parameters in human for dosing regimens selected by the client.

Multi-species in vivo PK represents a significant investment during lead optimization and pre-clinical development. Maximizing information extraction from the data is critical for reliable PK prediction, dose prediction and hence knowledge of likely outcomes in Phase I clinical trials. Cyprotex Modelling and Simulation staff will work with your pre-clinical data to generate robust human PK models that you can use to inform your subsequent development strategies, such as compound progression, further experimental prioritization and design, and human dose selection.