caa a22 4500 445313978 CHVBK 20180317142639.0 cr unu---uuuuu 170323e20110501xx s 000 0 eng 10.1007/s11095-010-0363-8 doi (NATIONALLICENCE)springer-10.1007/s11095-010-0363-8 Assessment of Pharmacologic Area Under the Curve When Baselines are Variable [Elektronische Daten] [Jeremy Scheff, Richard Almon, Debra DuBois, William Jusko, Ioannis Androulakis] ABSTRACT: Purpose: The area under the curve (AUC) is commonly used to assess the extent of exposure of a drug. The same concept can be applied to generally assess pharmacodynamic responses and the deviation of a signal from its baseline value. When the initial condition for the response of interest is not zero, there is uncertainty in the true value of the baseline measurement. This necessitates the consideration of the AUC relative to baseline to account for this inherent uncertainty and variability in baseline measurements. Methods: An algorithm to calculate the AUC with respect to a variable baseline is developed by comparing the AUC of the response curve with the AUC of the baseline while taking into account uncertainty in both measurements. Furthermore, positive and negative components of AUC (above and below baseline) are calculated separately to allow for the identification of biphasic responses. Results: This algorithm is applied to gene expression data to illustrate its ability to capture transcriptional responses to a drug that deviate from baseline and to synthetic data to quantitatively test its performance. Conclusions: The variable nature of the baseline is an important aspect to consider when calculating the AUC. Springer Science+Business Media, LLC, 2011 AUC nationallicence baseline nationallicence bioinformatics nationallicence microarrays nationallicence pharmacogenomics nationallicence Scheff Jeremy Biomedical Engineering Department, Rutgers University, 599 Taylor Road, 08854, Piscataway, New Jersey, USA aut Almon Richard Department of Biological Sciences, State University of New York at Buffalo, 14260, Buffalo, New York, USA aut DuBois Debra Department of Biological Sciences, State University of New York at Buffalo, 14260, Buffalo, New York, USA aut Jusko William Department of Pharmaceutical Sciences, State University of New York at Buffalo, 14260, Buffalo, New York, USA aut Androulakis Ioannis Biomedical Engineering Department, Rutgers University, 599 Taylor Road, 08854, Piscataway, New Jersey, USA aut Pharmaceutical Research Springer US; http://www.springer-ny.com 28/5(2011-05-01), 1081-1089 0724-8741 28:5<1081 2011 28 11095 https://doi.org/10.1007/s11095-010-0363-8 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s11095-010-0363-8 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Scheff Jeremy Biomedical Engineering Department, Rutgers University, 599 Taylor Road, 08854, Piscataway, New Jersey, USA aut NATIONALLICENCE 700 1- Almon Richard Department of Biological Sciences, State University of New York at Buffalo, 14260, Buffalo, New York, USA aut NATIONALLICENCE 700 1- DuBois Debra Department of Biological Sciences, State University of New York at Buffalo, 14260, Buffalo, New York, USA aut NATIONALLICENCE 700 1- Jusko William Department of Pharmaceutical Sciences, State University of New York at Buffalo, 14260, Buffalo, New York, USA aut NATIONALLICENCE 700 1- Androulakis Ioannis Biomedical Engineering Department, Rutgers University, 599 Taylor Road, 08854, Piscataway, New Jersey, USA aut NATIONALLICENCE 773 0- Pharmaceutical Research Springer US; http://www.springer-ny.com 28/5(2011-05-01), 1081-1089 0724-8741 28:5<1081 2011 28 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer