Gedmore brings PK-PD modeling to pharmaceutical research. PK-PD’s unique predictive capabilities are extensively used to support clinical decisions, but its wider implementation is hindered by the associated time and costs.
Gedmore’s aim is to change this. Gedmore applies modern web technology to offer tailored PK-PD modeling at highly reduced cost and turnaround time. Research can now leverage PK-PD to accelarate decision making and improve designs, too!
Gedmore is a system that automates PK-PD model development. Data are entered using an easy and graphical interface. Results are delivered in a practical report format that can be directly used in presentations or other forms of communication. Gedmore is available as a web application, comparable to Software-as-a-Service (SaaS) solutions. There is no install or any license commitment needed. You only pay for what you are using.
The scope of Gedmore’s initial release is the analysis of screening PK experiments. These experiments are typically conducted by dosing animals with a single dose of an investigational drug intravenously, and another group by the oral route. These data are than subjected to Gedmore’s proprietary model automation system. A combination of brute force calculuations and expert-system decisions is applied to develop models. The user is presented with the end-result in terms of ready-to-use simulations in a practical report.
The first step to get started is to enter your and your company’s information into this form. Upon receipt, an account will be created and than you are able to set your password via the “forgot your password” link of the log in screen. . To save costs and ensure a smooth experience, fees need to be paid on beforehand, see here for an overview. The first use is on us and the first time only a nominal amount of € 20.- needs to be transferred as an acceptance of Terms & Conditions including non-disclosure terms for your protection. Details on wiring etc. will be send with the reply to the webform. When these formalaties are completed, you can start!
The system is designed to be self-explanatory for pharmacokinetic scientists, and you can go ahead and use it rightaway. Or alternatively, you may read on to fully prepare.
The initial step in the app itself is to create a project. Projects hold experiments, now you are ready to create one! More information on how to create experiments and develop the models with Gedmore can be found on this page.
After the model development process has been completed by you or a colleague, the status of your experiment will change from “Draft” to “Completed”. A click on a completed experiment opens the report window. A report will be generated on the fly, initially with default values. These settings can be found on the top of the page. You can enter the minimum and maximum dose you are interested in, the number of dose levels you would like to examine (including the extremes), and the route of administration. You can also enter the number of simulation days you would like to see, and how many doses should be applied on each day (frequency). There is also a field that indicates the number of simulated datapoint. The more points are entered, the more accurate fast transitions are plotted but also the files become bigger and the plotting slower. The default number should suffice for most situations because the datapoints are distributed to where most transitions occur.
When you scroll down you can find the body of the report behind the main graph. There is a general description of Methods applied, and the Results include a tabular description. The report also includes a listing of the major assumptions underlying the reported model. Each PK-PD model has its own assumptions. Assumptions carry the scope of the model. The current Gedmore system estimates strictly linear PK models, and all the assumptions listed are a reflection of that. The simulations projected in the report are only valid of the PK remains linear (over dose, concentration and time). This assumption is true for the majority of small molecules in the pharmacological dose range.
The contents of the report can also be saved as a PDF. The PDF form is accessible with the print button. Browsers will provide the option to print to a PDF file. Standard settings are sufficient for most situations but can be adjusted in the browser’s print dialog.
The results of Gedmore can be used in many ways. Two applications of results obtained with Gedmore stand out:
1. Prioritize compounds on PK
Resources are always limited. If your team has delivered more compounds with roughly appropriate PK, you can prioritize them using Gedmore. You will know which of these compounds has the best before doing the follow-up experiments. Therefore you can save money or other resources by only performing multiple-dose experiments on the compounds with the best profile. For example, if you would screen 5 compounds, and on the basis of Gedmore’s results, remove 1 of them out of your flowchart, you are likely to gain at least 4 times on your investment. More importantly, you free up your resources to add value with another series or project.
2. Design the next experiment
Using Gedmore’s predicted profiles, you know on beforehand where to expect high and low concentrations. This will allow you to design your next experiment with much more confidence. You will have a much better idea of what dose levels to choose, how frequent to dose and at which times measurements would be useful. Such predictions will prevent a certain level of experimental failure because designs will be of higher quality.
As with all PK-PD modeling approaches, the results of Gedmore will certainly not have a perfect score. Users are encouraged to think along the 80/20% or 90/10% rule. Such guidelines are commonly applied in Drug Discovery, and convey the expectation that the outcome of an assay may be wrong 20% or 10% of the times. If you need a higher a higher accuracy than these rules indicate, please request expert human advice on those matters. With Gedmore premium, one hour of consultation per unit of experiment is included.