Pharmacokinetics and pharmacodynamics are divisions of pharmacology that study the action of the body on the drug and the action of the drug on the body, respectively.
The classical pharmacokinetic (PK)/pharmacodynamic (PD) studies are experimental; usually no benefit for treated subject is to be expected. They are most often performed on healthy volunteers or highly selected patients to minimize inter-individual variability. These studies allow to demonstrate a mechanism and to obtain rough quantitative information on the link between the dose and the effect (PK/PD behavior) of the drug. Our expert pharmacokinetic and pharmacodynamic data analysis services are available for non-clinical and clinical studies. Our experienced pharmacokineticists provide high quality PK/PD reports using either our standard format or producing them in the client guided formats.
We offer the following standard PK/PD analysis services and more:
- Developing PK/PD strategy as part of the drug development plan
- Designing standalone PK studies and sub-studies
- Sample size and power calculations
- Generation of randomization code
- Preparation of analysis plans
- Compartmental and non-compartmental pharmacokinetic analysis
- Pharmacodynamic analysis
- Assessment of PK/PD relationship
- Assessments of Bioequivalence/Bioavailability
- Drug interaction evaluations
- Reporting
Accelsiors is using WinNonlin©version 5.2.1 as the main tool for the PK/PD analysis as it is the industry standard for pharmacokinetic, pharmacodynamic, and non-compartmental analysis. In addition to its extensive library of built-in PK, PD and PK/PD models, WinNonlin supports custom, user-defined models to address any kind of data.
Population PK/PD studies quantify the effect of the drug on a population of patients who could use the drug. They allow quantifying, explaining, and predicting how the variability of the drug plasma concentration acts on the variability of the drug effect. They enable optimization (individualization) of dosage regimen. Usually performed on a sample of patients who are representative of the target population, they can be considered as observational studies.
Population PK/PD relies on the use of models. A model can be defined as a simplified description of reality. Most models used in population PK/PD are statistical models. These models describe observations (concentrations and effects), but may also give some outlines of the underlying biological process. Our PK team is very experienced in PK/PD modeling and simulations. The benefits of PK/PD modeling we offer can be summarized as follows:
- Integrate in a mechanism-based PK/PD model the time-course of IMP concentrations, PD markers and/or clinical responses
- Decrease drug development time & cost by:
- Exploring doses and dosing intervals via Monte Carlo simulation
- Rational selection of optimized dosage regimens for human clinical trials
- Fewer blood sampling at optimized time points in human trials (ethical benefit and cost saving; e.g. 6 instead of 12 samples per patient)
- Increased value of your drug development program due to a modeling-supported understanding of your product
- Estimate and account for potentially large between patient variability
- Predict the median response and distribution of responses via Monte Carlo simulation for the patient population.
- Understand the benefits of different dosing intervals and difference of investigational product formulations
- Test and account for influential covariate effects (such as baseline, age, sex or other parameters)
- Integrate data from various species and translate from animal to man and bridge between adults to children (while accounting for literature data!).
- Ability to individualize the dosage regimen of an individual patient using Bayesian methods
- ‘Validate’ the proposed optimal study design by simulating e.g. 200 clinical trials and performing 200 population PK/PD estimations. This validation can account for real-life issues such as lost samples, missed doses, deviations in recorded dosing or sampling times
Accelsiors is using different software for the PK/PD modeling and simulations among which the most robust are the WinNonlin© and NONMEM.
