Abstract
The area under a curve (AUC) of metabolite concentration or drug concentration over time has biological meaning in many situations, and the test of AUC equality among a set of different dosing regimens is often of interest. For the situation where the experimental unit must be sacrificed in order to obtain an estimate of the metabolite or drug concentration, it is noted that linear combinations of mean concentrations at time points for a particular dosing regimen can be used to estimate the AUC for that regimen. Contrasts among AUC estimates are readily constructed and tested within this derivation.
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References
C. M. Metzler. Bioavailability—A problem in equivalence,Biometrics 30:309–317 (1974).
W. J. Westlake. Use of statistical methods in evaluation ofin vivo performance of dosage forms,J. Pharm. Sci. 62:1579–1589 (1973).
R. Snyder, S. L. Longacre, D. Sammett, C. M. Witner, and J. J. Kocsis. Relationship between the toxicity and metabolism of benzene, In M. Mehlman (ed.),Carcinogenicity and Toxicity of Benzene, Princeton Scientific Publishers, Princeton, NJ, 1983.
J. D. Sun, R. F. Henderson, T. C. Marshall, Y. Cheng, J. S. Dutcher, J. A. Pickrell, J. L. Mauderly, F. F. Hahn, D. A. Banas, F. A. Seiler, and C. H. Hobbs. The inhalation toxicity of two commercial dyes: Solvent yellow 33 and solvent green 3,Fund. Appl. Toxicol. 8:358–371 (1987).
R. L. Burden, J. D. Faires, and A. C. Reynolds.Numerical Analysis, Prindle, Weber, & Schmidt, Boston, MA, 1978, chap. 5.
K. C. Yeh and K. C. Kwan. A comparison of numerical integrating algorithms by trapezoidal, Lagrange, and spline approximation,J. Pharmacokin. Biopharm. 6:79–98 (1978).
R. Miller.Simultaneous Statistical Inference, 2nd ed. Springer-Verlag, New York, 1981, chap. 1.
C. Fuchs and A. R. Sampson. Simultaneous confidence intervals for the general linear model,Biometrics 43:457–469 (1987).
P. Sabourin, W. Bechtold, L. Birnbaum, G. Lucier, and R. Henderson. Water-soluble benzene metabolites in F344/N Rats and B6C3F, mice during and following3H-benzene inhalation,Toxicologist 7:232 (1987).
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Bailer, A.J. Testing for the equality of area under the curves when using destructive measurement techniques. Journal of Pharmacokinetics and Biopharmaceutics 16, 303–309 (1988). https://doi.org/10.1007/BF01062139
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DOI: https://doi.org/10.1007/BF01062139