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

Diane D. Stadler; James F. Bale; Catherine A. Chenard; Charles J. Rebouche

doi:10.1016/S0026-0495(99)90013-6

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

Diane D. Stadler
, James F. Bale
, Catherine A. Chenard
, Charles J. Rebouche

Research output: Contribution to journal › Article › peer-review

19 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	74-79
Number of pages	6
Journal	Metabolism: Clinical and Experimental
Volume	48
Issue number	1
DOIs	https://doi.org/10.1016/S0026-0495(99)90013-6
State	Published - 1999
Externally published	Yes

Funding

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

Funders	Funder number
Author National Institutes of Health National Institutes of Health National Institutes of Health National Institutes of Health The Bev Hartig Huntington's Disease Foundation National Institutes of Health	RRO0059
National Center for Research Resources	M01RR000059
U.S. Public Health Service

ASJC Scopus subject areas

Endocrinology, Diabetes and Metabolism
Endocrinology

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10.1016/S0026-0495(99)90013-6

Cite this

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title = "Effect of long-term valproic acid administration on the efficiency of carnitine reabsorption in humans",

abstract = "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.",

author = "Stadler, \{Diane D.\} and Bale, \{James F.\} and Chenard, \{Catherine A.\} and Rebouche, \{Charles J.\}",

note = "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 {\textcopyright} 1999 by W.B. Saunders Company 0026-0495/99/4801-0013503.00/0",

year = "1999",

doi = "10.1016/S0026-0495(99)90013-6",

language = "English (US)",

volume = "48",

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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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JF - Metabolism: Clinical and Experimental

IS - 1

ER -

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

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