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Using Partial Area for Evaluation of Bioavailability and Bioequivalence

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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.

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ACKNOWLEDGMENTS

The opinions expressed in this article are those of the authors and do not necessarily represent the views or policies of the Food and Drug Administration. The authors would like to thank Drs. Mamata Gokhale, Diane Wang, and Michael Fossler for their assistance in data collection during the early phase of this work. The authors would also like to express their gratitude for the helpful comments made by the reviewers of this paper.

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Authors and Affiliations

  1. Office of Pharmaceutical Science Center for Drug Evaluation and Research Food and Drug Administration (FDA), 10903 New Hampshire Avenue, Building 51, Rm. 4108, Silver Spring, Maryland, 20993–0002, USA

    Mei-Ling Chen

  2. Office of Generic Drugs, Office of Pharmaceutical Science Center for Drug Evaluation and Research, FDA, Rockville, Maryland, USA

    Barbara Davit, Robert Lionberger, Zakaria Wahba & Lawrence X. Yu

  3. Office of Clinical Pharmacology, Office of Translational Sciences Center for Drug Evaluation and Research, FDA, Silver Spring, Maryland, USA

    Hae-Young Ahn

Authors
  1. Mei-Ling Chen
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  2. Barbara Davit
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  3. Robert Lionberger
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  4. Zakaria Wahba
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  5. Hae-Young Ahn
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  6. Lawrence X. Yu
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Correspondence to Mei-Ling Chen.

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Chen, ML., Davit, B., Lionberger, R. et al. Using Partial Area for Evaluation of Bioavailability and Bioequivalence. Pharm Res 28, 1939–1947 (2011). https://doi.org/10.1007/s11095-011-0421-x

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  • DOI: https://doi.org/10.1007/s11095-011-0421-x

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