Format

Send to

Choose Destination
Epilepsy Res. 2002 Mar;49(1):1-10.

Comparison of the bioavailability of unequal doses of divalproex sodium extended-release formulation relative to the delayed-release formulation in healthy volunteers.

Author information

1
Abbott Laboratories, 100 Abbott Park Road, Dept. R4PK, Bldg. AP13A, Abbott Park, IL 60064-6104, USA. sandeep.dutta@abbott.com

Abstract

Valproate formulations, divalproex sodium extended-release (ER) and the traditional divalproex sodium delayed-release (DR) formulations, are not bioequivalent. This study evaluated if ER QD regimens with 14 and 20% higher daily doses were equivalent to the corresponding DR BID regimens with respect to exposure (AUC) while achieving lower maximum concentration (C(max)) and higher minimum concentration (C(min)) values. This was a Phase I, multiple-dose, fasting, randomized, open-label, crossover design study in healthy adult volunteers (n=36). The two crossover comparisons of unequal total daily doses were: 1000 mg ER versus 875 mg DR and 1500 mg ER versus 1250 mg DR. For each of 14 and 20% higher ER versus DR dose comparisons, the ER and DR regimens were equivalent with respect to AUC. Furthermore, the ER formulation achieved a lower C(max) central value and a higher C(min) mean than the corresponding values for the DR formulation. The mean peak-to-trough fluctuations of valproic acid plasma concentrations were 42-48% lower for the ER formulation compared with the DR. The higher ER doses were as well tolerated as DR, with a small number of adverse events that were non-serious in nature and mild in intensity. Therefore, increasing the once-daily ER dose 14-20% while converting from a total daily DR dose given twice-daily results in equivalent exposure with lower C(max) and higher C(min) values.

PMID:
11948003
DOI:
10.1016/s0920-1211(02)00007-4
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center