Pharmaceutical Research

, Volume 11, Issue 7, pp 966–974 | Cite as

Bioequivalence: Performance of Several Measures of Rate of Absorption

  • Frédéric Y. Bois
  • Thomas N. Tozer
  • Walter W. Hauck
  • Mei-Ling Chen
  • Rabindra Patnaik
  • Roger L. Williams


The highest point of the plasma concentration-time profile, Cmax , is currently used by regulatory agencies to assess the rate of drug absorption after single dose administration of oral products. It is, however, quite insensitive, and a number of new measures of rate have been proposed. Using simulations, several approaches toward measuring rate were tested. A set of model scenarios for drugs with typical mean characteristics and statistical distributions was investigated. Using different kinetic models of disposition, the time course of the concentration in plasma was simulated. Intraindividual and interindividual variability and assay error were modeled using Monte Carlo techniques. The accuracy, precision, and ease of use of the various measures of rate were evaluated by simulating crossover design clinical trials and then determining the probability of declaring bioequivalence as a function of differences in rates of absorption between test and reference formulations. All of the rate measures tested showed a degree of insensitivity to changes in rate and no universally superior measure was found. Indeed, the main conclusion is that the choice of a measure should be based on simulations of the particular situation in a bioequivalence trials.


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Copyright information

© Plenum Publishing Corporation 1994

Authors and Affiliations

  • Frédéric Y. Bois
    • 1
  • Thomas N. Tozer
    • 2
  • Walter W. Hauck
    • 3
  • Mei-Ling Chen
    • 5
  • Rabindra Patnaik
    • 5
  • Roger L. Williams
    • 5
  1. 1.Indoor Environment ProgramLawrence Berkeley LaboratoryBerkeley
  2. 2.School of PharmacyUniversity of California San FranciscoSan Francisco
  3. 3.Department of Epidemiology and BiostatisticsUniversity of California San FranciscoSan Francisco
  4. 4.Dept. of Clinical PharmacologyJefferson Medical CollegePhiladelphia
  5. 5.Department of Health and Human Services, Food and Drug Administration.Center for Drug Evaluation and Research, Office of Generic DrugsRockville

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