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Sommerville KW, Dutta S, Biton V, et al. Bioavailability of a Divalproex Extended-Release Formulation versus the Conventional Divalproex Formulation in Adult Patients Receiving Enzyme-Inducing Antiepileptic Drugs. Clin Drug Investig. 2003;23(10):661-70doi: 10.2165/00044011-200323100-00005.
Sommerville, K. W., Dutta, S., Biton, V., Zhang, Y., Cloyd, J. C., & Uthman, B. (2003). Bioavailability of a Divalproex Extended-Release Formulation versus the Conventional Divalproex Formulation in Adult Patients Receiving Enzyme-Inducing Antiepileptic Drugs. Clinical drug investigation, 23(10), 661-70. https://doi.org/10.2165/00044011-200323100-00005
Sommerville, Kenneth W, et al. "Bioavailability of a Divalproex Extended-Release Formulation versus the Conventional Divalproex Formulation in Adult Patients Receiving Enzyme-Inducing Antiepileptic Drugs." Clinical drug investigation vol. 23,10 (2003): 661-70. doi: https://doi.org/10.2165/00044011-200323100-00005
Sommerville KW, Dutta S, Biton V, Zhang Y, Cloyd JC, Uthman B. Bioavailability of a Divalproex Extended-Release Formulation versus the Conventional Divalproex Formulation in Adult Patients Receiving Enzyme-Inducing Antiepileptic Drugs. Clin Drug Investig. 2003;23(10):661-70. doi: 10.2165/00044011-200323100-00005. PMID: 17535081.
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Clin Drug Investig. 2003;23(10):661-70. doi: 10.2165/00044011-200323100-00005.

Bioavailability of a Divalproex Extended-Release Formulation versus the Conventional Divalproex Formulation in Adult Patients Receiving Enzyme-Inducing Antiepileptic Drugs.

Clinical drug investigation

Kenneth W Sommerville, Sandeep Dutta, Victor Biton, Yiming Zhang, James C Cloyd, Basim Uthman

Affiliations

  1. Abbott Laboratories, Abbott Park, Illinois, USA.

PMID: 17535081 DOI: 10.2165/00044011-200323100-00005

Abstract

OBJECTIVES: To compare the bioavailability of divalproex extended release (divalproex-ER) given once daily relative to the conventional divalproex formulation given once every 8 hours, using various divalproex-ER doses that are 8-20% greater than the corresponding divalproex total daily doses.

DESIGN AND SUBJECTS: This multiple-dose, fasting, randomised, two-period, crossover design study in 76 subjects with epilepsy taking a concomitant enzyme-inducing antiepileptic drug compared the bioavailability of divalproex once-every-8-hours regimens with 8-20% higher daily dose divalproex-ER once-daily regimens.

RESULTS: The 8-20% higher divalproex-ER once-daily-dose regimens were equivalent, with respect to exposure (area under the concentration-time curve; 1551 vs 1539 mg . h/L), to the corresponding total daily divalproex dose regimens. The divalproex-ER maximum concentration central value was significantly lower (83.3 vs 92.6 mg/L), and the minimum concentration mean was not significantly different (45.8 vs 44.8 mg/L) from the corresponding values for the divalproex regimen. The peak-to-trough fluctuation in plasma concentrations was significantly lower for once-daily divalproex-ER (64%) compared with once-every-8-hours divalproex (79%). The size of the divalproex dose and the presence of a concomitant enzyme-inducing antiepileptic drug did not have a statistically significant effect on divalproex-ER/divalproex relative bioavailability. No adverse event occurred in more than 5% of subjects on either treatment; all were mild or moderate in severity with none resulting in discontinuation. Both tested formulations were well tolerated by the subjects.

CONCLUSION: This study demonstrated that patients with epilepsy taking divalproex may switch to 8-20% higher doses of divalproex-ER and have equivalent valproic acid exposure, lower fluctuation in valproic acid concentrations, and similar tolerability.

References

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