Comparison of the Bioavailability of Two Novel 250 mg Depakote Extended-Release Formulations Relative to a 500 mg Depakote Extended-Release Reference Formulation in Healthy Volunteers.
Abstract number :
1.279
Submission category :
Year :
2001
Submission ID :
262
Source :
www.aesnet.org
Presentation date :
12/1/2001 12:00:00 AM
Published date :
Dec 1, 2001, 06:00 AM
Authors :
S. Dutta, PhD, Clinical Pharmacokinetics, Abbott Laboratories, Abbott Park, IL; Y. Zhang, PhD, Clinical Statistics, Abbott Laboratories, Abbott Park, IL; D.S. Selness, BS, Clinical Pharmacology, Abbott Laboratories, Abbott Park, IL; L.L. Lee, MS, Clinical
RATIONALE: Depakote Extended-Release (ER), 500-mg strength, was recently approved for use in the prophylaxis of migraine. This study compared the bioavailabilty of two novel 250-mg ER formulations, under development to allow greater flexibility in dosing, to currently available 500-mg ER.
METHODS: This was a Phase I, single-dose, fasting and nonfasting, randomized, open-label, three-period, complete-crossover, single-center bioavailability study in healthy adult volunteers. One group of 15 subjects was dosed after a 10-hour fast and another group of 24 subjects was dosed after breakfast. The three treatments were: Depakote ER Formulation A (two 250-mg tablets, test), B (two 250-mg tablets, test), and C (one 500-mg tablet, reference). A washout interval of 7 days separated doses. Valproic acid (VPA) plasma concentration-time profiles were used to assess pharmacokinetics. Bioequivalence assessments were made via a 90% confidence interval (CI) for C[sub]max[/sub] and AUC[sub][infinity][/sub]. Safety was evaluated based on adverse event query, physical examinations, vital signs, and laboratory tests assessments.
RESULTS: Mean[plusminus]SD VPA pharmacokinetic parameters, and the point estimates and 90% CIs for ratios of formulation central values were:[Table]All three formulations were equally well tolerated, with a small number of adverse events that were non-serious in nature and mild in intensity.
CONCLUSIONS: Formulation B was bioequivalent, but Formulation A was not bioequivalent to reference Formulation C, under both fasting and nonfasting conditions. The formulations tested were generally well tolerated by the subjects. There were no apparent differences among the formulations with respect to safety.
Support: Abbott Laboratories
Disclosure: Salary - Abbott Laboratories