Single-dose kinetics and bioavailability of sodium-hydrogen divalproate.

Sodium-hydrogen divalproate (SHD) is a new chemical entity that quickly dissociates into valproic acid (VPA) and sodium valproate in water and is absorbed as VPA from the gastrointestinal tract. SHD is formulated as an enteric-coated tablet and may also result in less gastrointestinal irritation than other preparations of VPA. The bioavailability of valproate from SHD enteric-coated tablets (Epival, Abbott-50711) and from sodium valproate enteric-coated tablets (Ergenyl) was compared in a single-dose, double-blind, crossover study. Fourteen healthy volunteers (mean age 28.7 years) participated. A single oral dose of 250 mg SHD (assayed potency 249.3 mg VPA) or 300 mg sodium valproate (assayed potency 251.1 mg VPA) was given to each volunteer. Blood samples were collected intermittently up to 48 h and VPA in serum was assayed by gas chromatography. The areas under the serum concentration-time curves (AUC0----infinity) did not show any statistically significant difference (2,925.0 +/- 189.1 versus 2,816.2 +/- 162.2 h X mumol/L) between SHD and sodium valproate. The elimination parameters for SHD were t1/2 = 12.6 +/- 0.7 h and CLs = 0.008 +/- 0.0005 L/kg/h. Vd,area was 0.146 +/- 0.004 L/kg. Data for sodium valproate were not significantly different. Thus, the extent of bioavailability and the single-dose kinetics of SHD and sodium valproate are similar with the exception of a more rapid absorption (Tmax 2.37 versus 3.23 h) and a higher concentration (Cmax 192 versus 176 mumol/L) for SHD. Both of these differences were statistically significant (p less than 0.01).

RCT Entities:   Population Interventions Outcomes