| Metrics comparing simulated early concentration profiles for the determination of bioequivalence. | |
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MedLine Citation:
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PMID: 9706064 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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PURPOSE: To compare the effectiveness of various metrics which evaluate bioequivalence in the early phase of concentration-time profiles. METHODS: Two-period crossover trials were simulated with increasing assumed ratio of the true absorption rate constants of the two formulations, and with various kinetic models. Kinetic sensitivities (KS) and standard errors (SE) of the various metrics were recorded and the percentage of trials accepting bioequivalence (the statistical power) was evaluated. The principal metrics included the partial AUC(AUCP), the intercept obtained by linear extrapolation of the ratios of the lower over higher concentrations (C) measured for the two formulations (I L/H), and the ratios of intercepts extrapolated from logarithmic C/ time values of the two products (MLOG). For comparison, also properties of CMAX and an ideally evaluated measure (Id) were determined. RESULTS: MLOG showed generally the highest statistical power and KS, and also the largest SE, closely followed by I L/H. Partial AUC exhibited lower power and KS, but also smaller SE than the intercept procedures. The three methods had much higher power, KS and SE than CMAX. These comparisons were maintained over various kinetic conditions and experimental designs. The effective evaluation of bioequivalence in the early phase of studies is assured with 3 (or more) measurements until the population average peak of the reference formulation. CONCLUSIONS: The three principal methods assess bioequivalence very effectively in the early phase of a concentration-time profile. MLOG had the highest statistical power, closely followed by I L/H and then by partial AUC. |
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Authors:
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L Endrenyi; F Csizmadia; L Tothfalusi; M L Chen |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Pharmaceutical research Volume: 15 ISSN: 0724-8741 ISO Abbreviation: Pharm. Res. Publication Date: 1998 Aug |
Date Detail:
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Created Date: 1998-10-20 Completed Date: 1998-10-20 Revised Date: 2007-11-15 |
Medline Journal Info:
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Nlm Unique ID: 8406521 Medline TA: Pharm Res Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 1292-9 Citation Subset: IM |
Affiliation:
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Department of Pharmacology, University of Toronto, Ontario, Canada. l.endreyni@utoronto.ca |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Area Under Curve Evaluation Studies as Topic Pharmacokinetics* Therapeutic Equivalency |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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