In Vitro In Vivo Extrapolation using Cloe PK
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A tool for integrating in vitro ADME data to predict plasma and organ pharmacokinetics |
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Multispecies pharmacokinetic simulation from in vitro ADME and phys-chem data
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Predict pharmacokinetics from the integration of ADME and physicochemical data.
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Interprets ADME data and prioritises compounds for in vivo studies or candidate selection.
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Save time and cost by reducing unnecessary in vivo PK studies.
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Cloe PK data requirements
A simple set of early ADME and physicochemical data is required to run a Cloe PK simulation. Either measured or predicted values can be used.
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Data requirements for intravenous dosing |
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LogP (octanol/water) and pKa
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Microsomal intrinsic clearance
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Fraction unbound in plasma
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Blood to plasma ratio (optional)
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Data requirements for oral dosing |
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LogP (octanol/water) and pKa
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Microsomal intrinsic clearance
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Fraction unbound in plasma
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Blood to plasma ratio (optional)
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Aqueous solubility
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Caco-2 permeability
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Cloe PK data delivery
Predictions are delivered automatically in a downloadable pdf report and Excel spreadsheet with interactive
sensitivity analysis capability.
The following parameters are reported:
• Concentration time profiles in venous and arterial plasma.
• Concentration time profiles in 14 organs and tissues.
• Summary pharmacokinetic parameters
Options for using Cloe PK
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Additional Features |
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• 3 species, human PK prediction, rat PK prediction and mouse PK prediction, now available.
• Simple and easy to use.
• Interactive sensitivity analysis to investigate impact of altering one or more compound properties on the
predicted PK parameters.
• Access through our online web portal, Cloe Gateway, www.cloegateway.com, via pay per use or license agreement.
• Send your data to Cyprotex, and let us run predictions on your behalf.
• Provision of full consultancy service for interpretation of any predictions generated.
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Data from Cloe PK
Cloe PK integrates ADME data derived from experimental assays or QSAR predictive models using PBPK modelling techniques. The input data are limited to ADME and physicochemical properties that are typically generated in early drug discovery programs.
Prediction accuracy and compound ranking closely correlates with human clinical data and animal experiments.
Figure 1
Human steady state volume of distribution derived from Cloe PK (y-axis) are compared with clinical data (x-axis).
Figure 2
Rat half life derived from Cloe PK (y-axis) are compared with preclinical data (x-axis).
For a set of known drugs, the human steady state volume of distribution is predicted within an average of 1.9 fold of the measured values with a rank correlation of 0.83 and the rat half-life is predicted within an average of 1.6 fold of the measured values with a rank correlation coefficient of 0.88. For a set of 75 discovery compounds, the rat clearance is predicted within an average of 2.0 fold of the measured values (standard well stirred model = 4.3).
Figure 3
Comparison of Cloe PK predicted plasma concentration profiles with actual measurements from a human in vivo study for clozapine (intravenously administered).
Figure 4
Comparison of Cloe PK predicted plasma concentration profiles with actual measurements from a rat in vivo study for chlorpheniramine (orally administered).
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Three main options exist for gaining access to Cloe PK: |
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Pay per use – You can pre-purchase credits online which can be used to access Cloe PK through the Cloe Gateway web portal. This is a cost effective option for users who only require occasional use of Cloe PK.
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License – This allows unlimited access to Cloe PK via either a single user or site license. This is the most cost effective option if you use Cloe PK regularly.
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Consultancy – Cyprotex can run the predictions on your behalf. You can either send us your data or we can generate data for you via our Cloe Screen or Cloe Select experimental service. Assistance in interpreting the data is included in this service.
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Cloe® is a registered trade mark owned by Cyprotex PLC
