Relative bioavailability of different valproic acid formulations

Area of Science:

• Pharmacology
• Clinical Pharmacy
• Drug Development

Background:

• Valproic acid is a widely used antiepileptic drug.
• Ensuring the bioavailability of generic formulations is crucial for therapeutic equivalence.
• Convulsofin (test) and two reference formulations (ref.A, ref.B) were compared.

Purpose of the Study:

• To assess the relative bioavailability of valproic acid from Convulsofin tablets compared to two reference formulations.
• To determine bioequivalence regarding the extent and rate of absorption.

Main Methods:

• A controlled, randomized, 3-period crossover clinical trial in 16 healthy volunteers.
• Oral administration of Convulsofin tablets versus reference dragees and liquid formulations.
• Serum valproic acid levels measured using Gas Chromatography (GC).
• Pharmacokinetic analysis using compartment-free methods.

Main Results:

• Convulsofin demonstrated bioequivalence with both ref.A and ref.B based on AUC and Cmax/AUC ratios.
• The 90% confidence intervals for AUC ratios (test/ref.A, test/ref.B) were within the 0.80-1.25 range.
• The 90% confidence intervals for Cmax/AUC ratios (test/ref.A, test/ref.B) were within the 0.70-1.43 range.
• Convulsofin showed a faster rate of absorption (tmax) compared to ref.A, but slower than ref.B.

Conclusions:

• Convulsofin tablets are bioequivalent to the reference formulations (ref.A and ref.B) in terms of the extent of valproic acid absorption.
• While bioequivalent, differences in the rate of absorption (tmax) were observed between the test and reference products.