caa a22 4500 445313544 CHVBK 20180317142638.0 cr unu---uuuuu 170323e20110801xx s 000 0 eng 10.1007/s11095-011-0421-x doi (NATIONALLICENCE)springer-10.1007/s11095-011-0421-x Using Partial Area for Evaluation of Bioavailability and Bioequivalence [Elektronische Daten] [Mei-Ling Chen, Barbara Davit, Robert Lionberger, Zakaria Wahba, Hae-Young Ahn, Lawrence Yu] ABSTRACT: Assessment of bioavailability/bioequivalence generally relies on the comparison of rate and extent of drug absorption between products. Rate of absorption is commonly expressed by peak concentration (Cmax) and time to peak concentration (Tmax), although these parameters are indirect measures of absorption rate. Recognizing the importance of systemic exposure to drug efficacy and safety, FDA recommended that systemic exposure be better used for bioavailability/bioequivalence assessment. Apart from peak exposure and total exposure, FDA also recommended a new metric for early exposure that is considered necessary when a control of input rate is critical to ascertain drug efficacy and/or safety profile. The early exposure can be measured by truncating the area under the curve at Tmax of the reference product (PAUCr,tmax) or some designated early time after dosing. The choice of truncation is most appropriately based on PK/PD relationship or efficacy/safety data for the drug under examination. Compared with Cmax, PAUCr,tmax has higher sensitivity in detecting formulation differences and may be more variable. If the metric is highly variable, the reference-scaling approach can be employed for bioequivalence evaluation. The partial area metric is useful in PK/PD characterization as well as in the evaluation of bioavailability, bioequivalence and/or comparability. Springer Science+Business Media, LLC (outside the USA), 2011 bioavailability/bioequivalence nationallicence early exposure nationallicence partial area nationallicence partial AUC nationallicence truncated area nationallicence Chen Mei-Ling Office of Pharmaceutical Science Center for Drug Evaluation and Research Food and Drug Administration (FDA), 10903 New Hampshire Avenue, Building 51, Rm. 4108, 20993-0002, Silver Spring, Maryland, USA aut Davit Barbara Office of Generic Drugs, Office of Pharmaceutical Science Center for Drug Evaluation and Research, FDA, Rockville, Maryland, USA aut Lionberger Robert Office of Generic Drugs, Office of Pharmaceutical Science Center for Drug Evaluation and Research, FDA, Rockville, Maryland, USA aut Wahba Zakaria Office of Generic Drugs, Office of Pharmaceutical Science Center for Drug Evaluation and Research, FDA, Rockville, Maryland, USA aut Ahn Hae-Young Office of Clinical Pharmacology, Office of Translational Sciences Center for Drug Evaluation and Research, FDA, Silver Spring, Maryland, USA aut Yu Lawrence Office of Generic Drugs, Office of Pharmaceutical Science Center for Drug Evaluation and Research, FDA, Rockville, Maryland, USA aut Pharmaceutical Research Springer US; http://www.springer-ny.com 28/8(2011-08-01), 1939-1947 0724-8741 28:8<1939 2011 28 11095 https://doi.org/10.1007/s11095-011-0421-x text/html Onlinezugriff via DOI 1 review-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s11095-011-0421-x text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Chen Mei-Ling Office of Pharmaceutical Science Center for Drug Evaluation and Research Food and Drug Administration (FDA), 10903 New Hampshire Avenue, Building 51, Rm. 4108, 20993-0002, Silver Spring, Maryland, USA aut NATIONALLICENCE 700 1- Davit Barbara Office of Generic Drugs, Office of Pharmaceutical Science Center for Drug Evaluation and Research, FDA, Rockville, Maryland, USA aut NATIONALLICENCE 700 1- Lionberger Robert Office of Generic Drugs, Office of Pharmaceutical Science Center for Drug Evaluation and Research, FDA, Rockville, Maryland, USA aut NATIONALLICENCE 700 1- Wahba Zakaria Office of Generic Drugs, Office of Pharmaceutical Science Center for Drug Evaluation and Research, FDA, Rockville, Maryland, USA aut NATIONALLICENCE 700 1- Ahn Hae-Young Office of Clinical Pharmacology, Office of Translational Sciences Center for Drug Evaluation and Research, FDA, Silver Spring, Maryland, USA aut NATIONALLICENCE 700 1- Yu Lawrence Office of Generic Drugs, Office of Pharmaceutical Science Center for Drug Evaluation and Research, FDA, Rockville, Maryland, USA aut NATIONALLICENCE 773 0- Pharmaceutical Research Springer US; http://www.springer-ny.com 28/8(2011-08-01), 1939-1947 0724-8741 28:8<1939 2011 28 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer