Effects of three antacids on the bioavailability of valproic acid

The effects of three antacid products on the bioavailability of valproic acid were evaluated. Each of seven normal, healthy volunteers received a 500-mg dose of valproic acid alone on one occasion and then with each of three commonly used antacids. Specifically, equal neutralizing capacity doses of 160 meq of Maalox (62 ml), Trisogel (97 ml), or Titralac (42 ml) were administered one and three hours after meals and at bedtime on the same day. Blood samples were obtained at 0, 1, 2, 4, 6, 8, 10, 24, and 32 hours and analyzed for valproic acid by gas liquid chromatography. There was a significant increase in total area under the curve (AUC) (range 3% to 28%, mean 12%) when valproic acid was administered with Maalox (p = 0.026 for total AUC and p = 0.009 for AUC to 32 hours). There was an insignificant trend toward an increase in AUC when valproic acid was administered with the other two antacids. No differences were observed in time to peak serum concentration, height of peak serum concentration, volume of distribution, half-life, or first order elimination rate constant. Caution should be exercised if valproic acid and antacids are administered concomitantly.