title: Using partial area for evaluation of bioavailability and bioequivalence.
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 (C(max)) and time to peak concentration (T(max)), 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 T(max) of the reference product (PAUC(r,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 C(max), PAUC(r,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.
authors.affiliation: Office of Pharmaceutical Science Center for Drug Evaluation and Research Food and Drug Administration, 10903 New Hampshire Avenue, Building 51, Rm. 4108, Silver Spring, Maryland 20993-0002, USA. meiling.chen@fda.hhs.gov
authors.forename: Mei-Ling
authors.initials: ML
authors.lastname: Chen
authors.forename: Barbara
authors.initials: B
authors.lastname: Davit
authors.forename: Robert
authors.initials: R
authors.lastname: Lionberger
authors.forename: Zakaria
authors.initials: Z
authors.lastname: Wahba
authors.forename: Hae-Young
authors.initials: HY
authors.lastname: Ahn
authors.forename: Lawrence X
authors.initials: LX
authors.lastname: Yu
mesh_terms: D019540:Area Under Curve; D001682:Biological Availability; D006801:Humans; D013810:Therapeutic Equivalency; D014481:United States; D014486:United States Food and Drug Administration