Pharmacokinetics / Pharmacodynamics / Pharmacometrics

Pharmacokinetics (PK) characterizes the movement of a drug through the body, with parameters describing its absorption, distribution, bioavailability, metabolism, and excretion over time. Pharmacodynamics (PD) characterizes the body’s response to the drug and is often described by biochemical or molecular interactions or physiological effects of a drug. Understanding the exposure-response relationship (PK/PD) is key to the development and approval of every drug. PK and PD analyses are used to characterize drug exposure, predict dosage requirements, assess changes in dosage requirements, estimate rate of elimination and rate of absorption, calculate relative bioavailability / bioequivalence, characterize intra- and inter-subject variability, to know concentration-effect relationships, establish safety margins and efficacy characteristics Noncompartmental analyses (GLP and Non-GLP), Modeling and simulation (compartmental and population PK models), Preclinical ADME and human studies, First-Time-in-Human (FTIH), Drug-Drug Interaction (DDI), Thorough QT (TQT) Study, Site of Absorption, Dosing simulations, Risk analysis, Integrated clinical/PK study are some of analysis done during PK/PD studies. PK & PD support in pre-clinical and Phase I-III clinical studies in accordance with international regulatory standards (FDA, EMEA, ICH) is mostly done by major CRO’s globally. Scientific PK/PD Consulting Services include PK/PD input into the protocol and the SAP, Modelling and simulation, Population PK/PD modelling (including covariates assessment), Statistical analysis of PK and PD outcomes, Analysis of pre-clinical and clinical PK data, The attrition rate in the pharmaceutical industry remains high, with a Phase III failure rate of 40 to 50%. In an attempt to address this issue, there is now a larger emphasis on quantitative predictions and translational science from the early exploratory stage through pre-clinical development and into the clinical arena. This has led to a greater use of pharmacokinetic (PK) and pharmacodynamic (PD) data analysis, to better understand a drug's mechanism of action, efficacious dose size and therapeutic index. This information allows pharmaceutical companies to make better decisions earlier and select drug candidates with the greatest chances of success, thus increasing the success rate during late-stage clinical trials Software tools such as of WinNonLin Phoenix and Unix SAS for Non-Compartmental Analysis or Compartmental Analysis , PDx-Pop® integrating NONMEM®, -R and MS Excel® for expedited population PK/PD, modelling and simulation analysis, Sigmaplot facilities, for macro creation and statistical reporting offer an upper hand during these studies. PK-PD modelling (pharmacometrics or quantitative pharmacology) is the science of developing simplified computer-based models that provide useful mechanistic understanding of the processes involved in drug disposition and corresponding therapeutic effect as a function of time. Study of plasma concentration-time profile (pharmacokinetics, PK) and understanding the quantitative link to therapeutic response (PK-PD) of a drug is of prime importance for selection of the optimal dosage and frequency to treat patients and minimise unwanted adverse events. Pediatric Pharmacometric Services include pediatric PK/PD modeling and simulation, Study design optimization and clinical trial simulations, extensive covariate analysis, pediatric optimal sampling strategies, physiologically based PK/PD modelling, exposure, efficacy and safety assessment. Non-linear mixed effects - or "population" PK-PD - modelling allows for analysis of both the population mean response in addition to description and explanation of inter-individual differences in therapeutic response and characterization of residual variability in studies. Population PK-PD models can be used for simulation of study trial outcome with different dosage regiments.PK-PD models based on translational biomarkers is a useful tool to predict patient response based on experimental disease models and hence it is a strong analytical tool that plays an increasing role in drug research & development in the pharmaceutical industry. PK-PD modelling is applicable to a wide range of pharmacological areas and can be used to analyse data from both animal and human studies.During drug development in pharmaceutical industry, pharmacometrics is applied to facilitate selection of compounds to enter clinical development, to support optimisation of drug formulations and CMC processes, and to optimise clinical study designs (including dose selection). Through PK / PD modelling and simulation, these techniques are also used to bridge different study populations (e.g. from healthy volunteers to pediatrics) and to facilitate strategic project decisions (go – no go). Nowadays pharmacometrics is widely applied in all stages of drug development and is an integral part of the regulatory dossier. Guidelines to perform such analysis including population pharmacokinetics have been released by the FDA and EMA. Clinical pharmacokinetics (PK) and toxicokinetics (TK) services involve allometric scaling, exploratory PK/PD analysis, programming NONMEM datasets, modelling and simulation software and population pharmacokinetics.