TY - JOUR
T1 - Effect of long-term valproic acid administration on the efficiency of carnitine reabsorption in humans
AU - Stadler, Diane D.
AU - Bale, James F.
AU - Chenard, Catherine A.
AU - Rebouche, Charles J.
N1 - Funding Information:
From the Program in Human Nutrition, Department of Pediatrics, and General Clinical Research Center, University of Iowa College of Medicine, Iowa City, IA. Submitted February 6, 1998; accepted June 28, 1998. Supported by Sigma-tau Pharmaceuticals, Children's Miracle Network Telethon, and US Public Health Service Grant No. NIH RRO0059. Present address: D.D.S., Division of Foods and Nutrition, College of Health, University of Utah, Salt Lake City, UT 84112; J.EB., Department of Pediatrics, College of Medicine, University of Utah, Salt Lake City, UT84112. Address reprint requests to Charles J. Rebouche, PhD, Department of Pediatrics, 2501 Crosspark Rd, Coralville, IA 52241. Copyright © 1999 by W.B. Saunders Company 0026-0495/99/4801-0013503.00/0
PY - 1999
Y1 - 1999
N2 - To elucidate the etiology of valproic acid-induced carnitine deficiency, we tested the hypothesis that long-term valproic acid administration decreases the rate of carnitine reabsorption. Thirteen healthy men participated in a 34-day protocol in which carnitine clearance was measured before and after 28 days of valproic acid administration. During valproic acid administration (days 6 to 33), plasma free and total carnitine concentrations decreased (18% and 12%, respectively, P < .05) by 16 days, but returned to pretreatment concentrations by 28 days. From day 14 to day 30, the rate of free carnitine excretion was 50% lower than at baseline (day 4, P < .05). Free and total carnitine clearance, indexed to the glomerular filtration rate, was lower after valproic acid administration (P < .01). Contrary to our hypothesis, after 28 days of valproic acid administration, the rate of carnitine reabsorption was enhanced independent of the glomerular filtration rate and filtered load. Changes in the plasma concentration, rate of excretion, and clearance were specific for carnitine and were not generalized in magnitude or direction to the other amino acids. We conclude that the kidney adapts to conserve carnitine during valproic acid administration and therefore does not cause valproic acid-induced carnitine depletion in adults.
AB - To elucidate the etiology of valproic acid-induced carnitine deficiency, we tested the hypothesis that long-term valproic acid administration decreases the rate of carnitine reabsorption. Thirteen healthy men participated in a 34-day protocol in which carnitine clearance was measured before and after 28 days of valproic acid administration. During valproic acid administration (days 6 to 33), plasma free and total carnitine concentrations decreased (18% and 12%, respectively, P < .05) by 16 days, but returned to pretreatment concentrations by 28 days. From day 14 to day 30, the rate of free carnitine excretion was 50% lower than at baseline (day 4, P < .05). Free and total carnitine clearance, indexed to the glomerular filtration rate, was lower after valproic acid administration (P < .01). Contrary to our hypothesis, after 28 days of valproic acid administration, the rate of carnitine reabsorption was enhanced independent of the glomerular filtration rate and filtered load. Changes in the plasma concentration, rate of excretion, and clearance were specific for carnitine and were not generalized in magnitude or direction to the other amino acids. We conclude that the kidney adapts to conserve carnitine during valproic acid administration and therefore does not cause valproic acid-induced carnitine depletion in adults.
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U2 - 10.1016/S0026-0495(99)90013-6
DO - 10.1016/S0026-0495(99)90013-6
M3 - Article
C2 - 9920148
AN - SCOPUS:0032899195
SN - 0026-0495
VL - 48
SP - 74
EP - 79
JO - Metabolism: Clinical and Experimental
JF - Metabolism: Clinical and Experimental
IS - 1
ER -