Evaluation of different partial AUCs as indirect measures of rate of drug absorption in comparative pharmacokinetic studies.
The performance of different partial AUCs, including partial AUC from zero to t(max) of the reference formulation (AUC(r)) and partial AUC from zero to tmax of test or reference formulation, whichever occurs earliest (AUC(e), as indirect measures of rate of absorption have been evaluated using simulated experiments. The performance of these metrics relative to C(max), t(max) and C(max)/AUC(infinity) was further assessed using the results of actual studies involving a Glaxo drug. The normalised metrics AUC(r)/AUC(infinity) and AUC(e)/AUC(infinity) have also been evaluated. Our provisional conclusions were: (1) AUC(r)/AUC(infinity) and AUC(e)/AUC(infinity) had greater statistical power than C(max) and the non-normalised partial AUCs at detecting true differences in rate of absorption. Using real data, the performance of AUC(e)/AUC(infinity) was poor, however, the performance of AUC(r)/AUC(infinity) was good; (2) C(max)/AUC(infinity) was more precisely estimated than AUC(r)/AUC(infinity) or AUC(e)/AUC(infinity) and may be a superior metric for assessing absorption rates of highly variable drugs.
Duquesnoy
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Department of Clinical Pharmacology, Laboratoire Glaxo Wellcome, 20, rue Rouget de Lisle, 92 442 Issy les Moulineaux Cedex, France.
Lacey
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Keene
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ON
Bye
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A
D019540:Area Under Curve; D003198:Computer Simulation; D007408:Intestinal Absorption / Q000502:physiology*; D015233:Models, Statistical; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D010599:Pharmacokinetics; D013810:Therapeutic Equivalency
D004364:Pharmaceutical Preparations