Effect of chronic valproic acid treatment on plasma and urine carnitine levels in children: decreased urinary excretion.

Plasma levels and urinary carnitine excretion rates were determined in children treated with valproic acid (n = 11) and in age and sex matched controls (n = 11). Urine was collected throughout two consecutive 24 h periods in both groups, and blood samples were taken on the first day of collection after an overnight fast. The plasma level of total and free carnitine was significantly lower in the treated group (24.3 +/- 2.2 vs 34.9 +/- 2.4 and 16.8 +/- 1.8 vs 26.5 +/- 2.1 nanomol/ml; values are means +/- SEM), while there was no significant alteration in the acylcarnitine fraction. In the treated group of children a significant reduction was found in the plasma beta-hydroxybutyrate level indicating a limited fatty acid utilization (23.2 +/- 2.5 vs 81.9 +/- 7.8 nanomol/ml). Urinary total and free carnitine decreased from 286.4 +/- 57.8 to 120.8 +/- 18.2 and from 154.3 +/- 33.6 to 21.2 +/- 5.8 mumol/day, respectively; the acyled fraction was not significantly reduced. In one child, urinary carnitine excretion was followed during the first ten days of treatment. After the 2nd day a decrease of the total and free fraction was observed, confirming previous data obtained during chronic VPA treatment. It has been concluded that the decreased plasma carnitine associated with chronic VPA treatment is not a result of an increased excretion rate, but more likely the consequence of a relatively insufficient endogenous carnitine synthesis. The decreased plasma BOB level probably due to limited fatty acid utilization might also be a metabolic consequence of depressed carnitine concentration.