Effect of long-term valproic acid administration on the efficiency of carnitine reabsorption in humans

To elucidate the etiology of valproic acid-induced carnitine deficiency, we tested the hypothesis that long-term valproic acid administration decrease s the rate of carnitine reabsorption. Thirteen healthy men participated in a 34-day protocol in which carnitine clearance was measured before and afte r 28 days of valproic acid administration. During valproic acid administrat ion (days 6 to 33), plasma free and total carnitine concentrations decrease d (18% and 12%, respectively, P <.05) by 16 days, but returned to pretreatm ent concentrations by 28 days. From day 14 to day 30, the rate of free carn itine excretion was 50% lower than at baseline (day 4, P <.05). Free and to tal carnitine clearance, indexed to the glomerular filtration rate, was low er after valproic acid administration (P <.01). Contrary to our hypothesis, after 28 days of valproic acid administration, the rate of carnitine reabs orption was enhanced independent of the glomerular filtration rate and filt ered load. Changes in the plasma concentration, rate of excretion, and clea rance were specific for carnitine and were not generalized in magnitude or direction to the other amino acids. We conclude:hat the kidney adapts to co nserve carnitine during valproic acid administration and therefore does not cause valproic acid-induced carnitine depletion in adults. Copyright (C) 1 999 by W.B. Saunders Company.