caa a22 4500 47712707X CHVBK 20180405111653.0 cr unu---uuuuu 170330e19971001xx s 000 0 eng 10.1023/A:1012160419520 doi (NATIONALLICENCE)springer-10.1023/A:1012160419520 Evaluation of Direct Curve Comparison Metrics Applied to Pharmacokinetic Profiles and Relative Bioavailability and Bioequivalence [Elektronische Daten] [S. Marston, James Polli] Purpose. The intent was to investigate three direct curve comparison metrics, the Rescigno Index,f1, and the Chinchilli Metric as tools to assess relative bioavailablity (BA) and bioequivalence (BE). The specific objectives were to 1) estimate relative bioavailability and bioequivalence and 2) compare detection of profile shape differences with typical (i.e. AUC and Cmax) criteria. Methods. Product bioequivalence was estimated and the degree of concordance with typical criteria in detecting profile differences was determined from the eighteen bioequivalence studies (390 subjects). Descriptive statistical analysis was carried out on the concordant and discordant profile subsets. Results. 1) Three of the eighteen studies failed typical criteria (AUC and Cmax). Of the curve metrics, 12 studies failed the Chinchilli metric criteria and 13 failed fl criteria. Using three different exponents in the Rescigno Index calculation, 17 (exponent = 3), 13 (exponent = 1), and 11 (exponent = 1/3) failed the criteria for bioequivalence. The frequency of profiles found to be different was comparable across the metrics, but the specific profiles found to be different or not different varied across the metrics. The Chinchilli Metric and fl agreed 71 % and 72% with typical criteria in judging profiles to be different or not different. Descriptive evaluation suggested that the direct curve metrics more effectively detect differences in absorption time lags but less effectively detect differences in Cmax. The Rescigno Index showed dependence on the direction of the difference between test and reference concentrations. Conclusions. With the limits used here, the direct curve metrics represent a more conservative approach to evaluate product bioequivalence. With further investigation and development, the direct curve approach may be used effectively to evaluate relative BA and BE. Plenum Publishing Corporation, 1997 bioequivalence metrics nationallicence bioequivalence nationallicence direct curve comparison nationallicence Marston S. Department of Pharmaceutical Sciences, University of Maryland, 20 N Pine St., 21201, Baltimore, Maryland aut Polli James Department of Pharmaceutical Sciences, University of Maryland, 20 N Pine St., 21201, Baltimore, Maryland aut Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/10(1997-10-01), 1363-1369 0724-8741 14:10<1363 1997 14 11095 https://doi.org/10.1023/A:1012160419520 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1023/A:1012160419520 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Marston S. Department of Pharmaceutical Sciences, University of Maryland, 20 N Pine St., 21201, Baltimore, Maryland aut NATIONALLICENCE 700 1- Polli James Department of Pharmaceutical Sciences, University of Maryland, 20 N Pine St., 21201, Baltimore, Maryland aut NATIONALLICENCE 773 0- Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/10(1997-10-01), 1363-1369 0724-8741 14:10<1363 1997 14 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer