Physiologically based pharmacokinetic models are being used in an increasing number of different areas. However, they are perceived as complex, data hungry, resource intensive, and time consuming. In addition, model validation and verification are hindered by the relative complexity of the equations. To begin to address these issues a web application called MEGen for the rapid construction and ...

This article is motivated by an application where subjects were dosed three times with the same drug and the drug concentration profiles appeared to be the lowest after the third dose. One possible explanation is that the pharmacokinetic (PK) parameters vary over time. Therefore, we consider population PK models with time-varying PK parameters. These time-varying PK parameters are modeled by na...

The concept of correlating pharmacokinetic parameters with body weight from different animal species has become a useful tool in drug development. The allometric approach is based on the power function, where the body weight of the species is plotted against the pharmacokinetic parameter(s) of interest. Clearance, volume of distribution, and elimination half-life are the three most frequently e...

To interpret pharmacokinetic (PK) data of biotherapeutics, it is critical to understand which drug species is being measured by the PK assay. For therapeutic antibodies, it is generally accepted that "free" circulating antibodies are the pharmacologically active form needed to determine the PK/pharmacodynamic (PD) relationship, safety margin calculations, and dose projections from animals to hu...

Genomic and other molecular factors frequently impact the efficacy, safety, and pharmacokinetic (PK) profiles of therapeutic products. Recent advances in our understanding of how these factors contribute to interindividual variability in drug response has led to the use of genomic strategies to improve clinical trial design in the drug development setting, and also to guide patient care in the ...

CONTEXT In a previous work, we have shown that penalized regression approaches can allow many genetic variants to be incorporated into sophisticated pharmacokinetic (PK) models in a way that is both computationally and statistically efficient. The phenotypes were the individual model parameter estimates, obtained a posteriori of the model fit and known to be sensitive to the study design. OBJ...

We present herein a compilation and trend analysis of human i.v. pharmacokinetic data on 670 drugs representing, to our knowledge, the largest publicly available set of human clinical pharmacokinetic data. This data set provides the drug metabolism scientist with a robust and accurate resource suitable for a number of applications, including in silico modeling, in vitro-in vivo scaling, and phy...

Conventional measures such as maximum plasma concentration (C max ) and area under the concentration versus time curve (AUC) may be insufficient to fully describe the pharmacokinetic (PK) profile of extended-release (ER) formulations. A complementary measure, the half-value duration (HVD), corresponds to the period of time during a dosing cycle that plasma concentration is at or above half the ...

The article presents an outline of the requirements concerning the planning of preclinical and clinical studies, necessary for the legal approval of a medicinal product. It describes the clinical research plan of innovative and generic pharmaceutical products, taking into account the specific situations in which the assessment of biological equivalence of a generic product is not possible based...