PK PD Analysis Study: Foundation of your eCTD FDA Submission

PK PD analysis study links drug exposure to therapeutic effect measures so drug developers can better understand the relationships between exposure, efficacy, and toxicity. Thus, PK PD assay and data analysis results are essential to any ECTD submission. Pharmacokinetics (PK) parameters are typically calculated by non-compartmental analysis (NCA) following the determination of test article concentrations in samples from clinical or preclinical studies. Generally, area under the curve (AUC) and maximum concentration (Cmax, or C0 for an IV dose) are accepted as the most critical PK parameters when discussing exposure and activity or toxicity. AUC in pharmacokinetics represents the total exposure of the test article over the tested time course. AUC can be extrapolated to infinity for well-designed studies. We derive absolute or relative bioavailability (F%) from the AUCs of multiple dose groups or administration routes. Scientists can readily obtain the Volume of distribution (Vz) and Clearance (CL) from a single IV dose. We can calculate specific PK parameters such as Volume of distribution at steady-state (Vss) and mean residence time (MRT) related to steady-state pharmacokinetics from a single dose using pharmacokinetic equations using statistical moment analysis. Thus, pharmacokinetic parameters help ascertain dose levels for PK PD modeling of drug exposure and efficacy in preclinical models of human disease, evaluate the impact of dose proportionality (linear or non-linear pharmacokinetics) on efficacy, toxicity, and therapeutic index, assess appropriate dosing intervals, and estimate clearance time in the case of serious adverse events or dose-limiting toxicities.

Compartmental vs. Non-Compartmental Analysis (NCA)

PK PD modeling is performed using non-compartmental analyses (NCA) or compartmental analysis. NCA allows for a model-independent interpretation of pharmacokinetic data using pre-defined equations. For individual studies in preclinical discovery through clinical development, non-compartmental analyses are often employed to characterize the pharmacokinetic data, offering the advantages of consistency of data for interpretation across multiple studies without any assumptions about compartment numbers or behaviors. Alternatively, compartmental analysis involves selecting a discrete number of bodily compartments that are connected and homogenously mixed. Here, the rates of drug flow in and out of each compartment are quantifiable. Physiologically based pharmacokinetic (PBPK) models are the most complex compartmental analyses, where all relevant organs and bodily systems represent compartments in the kinetic model. Typically, compartmental studies are utilized in population PK analyses with specific objectives to compare patient demographics and aid in decisions regarding dosing levels and frequencies to reach appropriate steady-state concentrations of drug in the body for suitable efficacy and minimal toxicity in differing population covariates. In all cases, well-designed PK PD studies are essential to obtain relevant data analysis to properly determine reliable kinetic parameters for correlation to efficacy and toxicity. Preclinical PK PD analysis helps select dose levels and regimens for pharmacology efficacy testing, and PK PD modeling helps scale preclinical results for preliminary predictions of clinical pharmacokinetics.

PK PD Study Services by NorthEast BioLab

NorthEast BioLab provides pharmacokinetic/pharmacodynamic (PK PD) study services from early drug discovery through clinical eCTD FDA submission and beyond. We offer end-to-end PK PD analysis services: in vitro ADME studies, bioanalytical method development, validation, and analysis of formulation and biological samples for test articles and metabolites. Additionally, we conduct non-compartmental analysis for pharmacokinetics of small molecules, proteins, peptides, antibodies (mab), etc. during preclinical and clinical studies in healthy subjects, models of preclinical disease, or clinical patients. We can help you interpret exposure and efficacy results to help you gain a clear understanding of your drug’s PK PD relationship. We perform compound screening, optimization, and characterization during drug discovery to improve DMPK properties and refine your screening cascade to lead compounds. We provide bioanalysis and toxicokinetic or pharmacokinetic evaluations using GLP/GCLP validated equipment, software, and methods during preclinical and clinical development. Our scientists are happy to assist you with project and protocol design, study prosecution, and data interpretation guidance at all project stages. We offer detailed audited study reports for sample bioanalysis and pharmacokinetics or toxicokinetics for drug discovery, development, and eCTD submissions. Additionally, we can put together Pharmacokinetic Concentration (PC) and Pharmacokinetic Parameter (PP) domains for your results in CDISC SDTM or SEND format for compliance with requirements for electronic submissions to the FDA and other global regulatory agencies. We maintain the latest and fully validated software packages for your PK data management and calculations, including Certara Phoenix WinNonlin, Watson LIMS, Sciex Analyst, Spectramax, etc.

Introduction to Pharmacokinetics

Pharmacokinetics (PK) is the analysis and description of the disposition of a drug in the body, encompassing development of the mathematical description of all dispositional processes in the body, defined as ADME – absorption, distribution, metabolism, and elimination…

Meticulous PK PD Analysis Study to Evaluate your Drug's True Potential

At NorthEast BioLab, our dedicated team of scientists has the necessary experience and expertise to assist with planning and executing your PK PD analysis, modeling, and reporting. Our assistance during lead optimization and characterization would help you get PK analysis right as a critical component of your drug discovery and development process. We compute AUC and Cmax pharmacokinetics to determine your drug compound’s systemic exposure, toxicity, and efficacy. We can evaluate PK from samples in your preclinical efficacy models from systemic circulation or tissues to help establish your dosing regimens and understand PK PD relationships. This PK PD modeling helps scientists and medics decide the correct drug dosage for early clinical trials. Hence, it is crucial to perform reliable, efficient PK PD studies and analysis to aid compound optimization in drug discovery. Similarly, we must carry out the GLP toxicology studies utilizing a fully validated and reliable bioanalytical and PK method to prepare for regulatory eCTD submissions. We offer formal and audited bioanalysis and pharmacokinetics reports and present your pharmacokinetic concentration and non-compartmental PK parameter results in compliant CDISC SEND or SDTM formats.

Related FAQs

Answers to additional Pharmacokinetic Pharmacodynamic (PK PD) Analysis questions popular among our potential clients.

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