ABSTRACT
I. Introduction.......................................................................................... 358
II. Bioavailability of a Single Formulation.............................................. 359
A. Compartmental Models................................................................. 359
B. Parameter Estimation.................................................................... 361
1. Individual Modeling................................................................ 361
2. Population Modeling............................................................... 364
III. Comparative Bioavailability Studies................................................... 366
A. Introduction ................................................................................... 366
B. Choice of the Criteria for Comparison......................................... 366
1. Area under the Concentration Curve...................................... 366
2. Peak Concentration (C
) ..................................................... 367
3. Time to Peak Concentration (T
)........................................ 367
4. Cumulative Percentage of Drug Recovered (A
) .................. 367
5. Estimated Absorption Rate (K
) ............................................. 367
6. Elimination Half-Life ............................................................. 367
7. Concentration Profiles............................................................. 368
C. Designing a Comparative Bioavailability Study.......................... 368
D. Sampling Times ............................................................................ 369
IV. Analysis of Comparative Bioavailability Studies ............................... 371
A. Analysis of Variance Model ......................................................... 371
B. The Power Approach .................................................................... 374
C. Confidence Interval Approach...................................................... 374
D. Bayesian Approach ....................................................................... 375
E. Anderson and Hauck’s Procedure ................................................ 375
F. Two One-Sided Tests Procedure .................................................. 376
G. Individual and Population Bioequivalence................................... 377
H. Choosing the Sample Size ............................................................ 381
I. Other Topics.................................................................................. 382
Acknowledgments ........................................................................................... 382
Appendix A. Peeling Technique for Obtaining Starting Values .................... 383
References........................................................................................................ 385
One of the steps necessary for characterizing a new drug dosage form is to conduct
an in vivo bioavailability study. The Food and Drug Administration (FDA)
requires that pharmaceutical companies perform these studies in order to produce
a new drug application (NDA) or an abbreviated new drug application (ANDA).
Specific details related to the requirements for an NDA are presented in the
Federal Register (January 7, 1977)
