April 25, 2016

Predictive Pharmacokinetic Modeling

Non-compartmental analysis provides useful and required information, but it is not always predictive outside the conditions of the study from which it was derived. PharmaDirections utilizes compartmental analysis to generate predictive models that can be used to streamline development and give you a better and more protectable product.

Model Development

PharmaDirections uses sophisticated software packages, such as WinNonLin® and GastroPlus® as well as internally developed tools to generate multi-compartmental models. We start with not only any PK data that are available but also various physico-chemical properties of the molecule as well as in vitro data to generate a comprehensive description of how the molecule is released from the dosage form, dissolves or precipitates in the gut, is absorbed, distributes throughout the body, and is metabolized and excreted.

We use as many data sets as are available and validate models generated with one data set against others. What we end up with is a model that not only describes what happens to the drug but can predict what will happen with other release profiles, with different dosing regimens, and even in different species.

Determining the Optimal Dosing Regimen

If you observe non-linear PK or very rapid clearance or significant accumulation in your preclinical or early clinical studies, it may not be obvious how best to dose your next study. In such cases we use predictive PK modeling to evaluate dosing paradigms and determine what will and will not work. This substantially de-risks the program, potentially leading to major cost and time savings.

Designing CR Dosage Forms

Zero order release is not always the ideal profile for a CR dosage form. With predictive PK modeling, we can work backward from the target plasma profile to generate an ideal release profile that becomes our target for formulation development.

Assessing Dosage Form Feasibility

Will an enteric-coated tablet do the trick? Is a controlled release product even feasible? These questions can always be answered in a clinical PK study, but by the time a dosage form is developed and tested, a lot of time and money has gone down the drain. Predictive PK modeling is an excellent tool to assess feasibility with relatively little time or cost outlay.

Intellectual Property Generation

Perhaps our most important and common use of predictive PK modeling over the years has been in generation of protective IP. In many cases the ideal release profile for a dosage form turns out not to be obvious, and when we figure out what it is, the patent we help you prepare can cover not just one CR dosage form but multiple formulation approaches used to meet the target.