Use of Partial AUC to Demonstrate Bioequivalence of Zolpidem Tartrate Extended Release Formulations.
Summary of "Use of Partial AUC to Demonstrate Bioequivalence of Zolpidem Tartrate Extended Release Formulations."
PURPOSE:
FDA's bioequivalence recommendation for Zolpidem Tartrate Extended Release Tablets is the first to use partial AUC (pAUC) metrics for determining bioequivalence of modified-release dosage forms. Modeling and simulation studies were performed to aid in understanding the need for pAUC measures and also the proper pAUC truncation times.
METHODS:
Deconvolution techniques, In Vitro/In Vivo Correlations, and the CAT (Compartmental Absorption and Transit) model were used to predict the PK profiles for zolpidem. Models were validated using in-house data submitted to the FDA. Using dissolution profiles expressed by the Weibull model as input for the CAT model, dissolution spaces were derived for simulated test formulations.
RESULTS:
The AUC(0-1.5) parameter was indicative of IR characteristics of early exposure and effectively distinguished among formulations that produced different pharmacodynamic effects. The AUC(1.5-t) parameter ensured equivalence with respect to the sustained release phase of Ambien CR. The variability of AUC(0-1.5) is higher than other PK parameters, but is reasonable for use in an equivalence test.
CONCLUSIONS:
In addition to the traditional PK parameters of AUCinf and Cmax, AUC(0-1.5) and AUC(1.5-t) are recommended to provide bioequivalence measures with respect to label indications for Ambien
CR:
onset of sleep and sleep maintenance.
Affiliation
Office of Generic Drugs, Office of Pharmaceutical Science Center for Drug Evaluation & Research, Food & Drug Administration, 7519 Standish Pl., Rockville, Maryland, 20855, USA, Robert.Lionberger@fda.hhs.gov.
Journal Details
This article was published in the following journal.
Name: Pharmaceutical research
ISSN: 1573-904X
Pages:
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/22278753
- DOI: http://dx.doi.org/10.1007/s11095-011-0662-8
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