Arzneimittelforschung 2008; 58(5): 255-258
DOI: 10.1055/s-0031-1296502
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Editio Cantor Verlag Aulendorf (Germany)

The Use of Truncated Area under the Curves in the Bioequivalence Evaluation of Long Half-Life Drugs

Studies with donepezil and memantine
Ülkem Erkent
1   Eczacibasi Pharmaceuticals Co., Istanbul, Turkey
Rossen Koytchev
2   Cooperative Clinical Drug Research and Development AG, Neuenhagen, Germany
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15. Dezember 2011 (online)


The bioequivalence of long terminal half-life drugs, donepezil (CAS 120014-06-4) 10 mg and memantine (CAS 19982-08-2) 10 mg, was evaluated by comparing the results obtained for the total areas under the concentration time curves (AUC(0–inf)) with those for partial AUCs: AUC(0–216h), AUC(0–72h) and AUC(0–48h). Pharmacokinetic endpoints were determined by standard formulas from the concentration-time courses of the parent compounds donepezil and memantine.

The results of the bioequivalence assessment based on the 90% confidence intervals calculated by means of ANOVA for logarithmically transformed values (ANOVA log) led to exactly the same decision irrespective of the type of AUC used. The 90% confidence intervals for all types of AUCs were practically identical within each product. These results prove that truncated AUCs, e.g. AUC(0–72h) or even AUC(0–48h), can be adequately used in assessing the relative bioavailability of long terminal half-life drugs. The findings suggest that even for drugs with half-lives between 24 and 60 h and thus shorter than those of donepezil and memantine an AUC truncated to 48 h post dose can be successfully used for the assessment of bioequivalence as this sample collection time ensures a proper comparison of the absorption process as recommended in the CPMP Note for Guidance on the Investigation of Bioavailability and Bioequivalence.

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