Some clinical pharmacological aspects of n-dipropylacetamide

The kinetics of the primary amide of valproic acid (VPA), i.e. dipropylacetamide, rapidly transformed into the corresponding acid in humans, are investigated and compared with valproate kinetics. In a group of healthy volunteers peak VPA concentration was reached within 5-14 hours of dipropylacetamide and within 1-2 hours of valproate administration. The plasma half-life appeared to be 8-12 hours for both compounds without significant differences. The relative bioavailability of the amide was 81.2% of valproate on average. In epileptics no correlation between plasma VPA levels and daily valproate or amide dose was observed; daily plasma valproic acid level fluctuations were significantly less wide during dipropylacetamide therapy. This compound seems to offer some advantages over sodium valproate, namely: slower absorption, stabler plasma levels through the day, 2 instead of 3 or 4 daily doses and hence less risk of drug defaulting.