title: Diet- and valproate-induced transient hyperammonemia: effect of L-carnitine.
abstract: Hyperammonemia is an adverse effect of valproate (VPA) treatment. In particular, transient hyperammonemia has been reported to occur in VPA-treated patients after protein-rich meals. This phenomenon may occur secondary to a VPA-mediated carnitine insufficiency. We sought to confirm that protein ingestion would result in transient hyperammonemia and to determine whether supplementation with L-carnitine would prevent this effect. We studied the effect of consumption of a standardized protein-rich meal (45 g protein) before (phase I) and after (phase II) administration of L-carnitine 50 mg/kg/day for 7 days in 11 epileptic children (13.3 +/- 2.3 years of age) receiving VPA. Venous blood was obtained during fasting (baseline) and at 2 and 4 hours after the protein-rich meal for analysis of ammonia (NH3), and VPA concentrations. Mean VPA trough concentrations did not differ significantly at any time. After protein ingestion, 2-hour NH3 concentration increased by 86% (P < .05) from baseline in phase I as compared with a 38% increase in phase II. In both phases I and II, 4-hour NH3 concentrations decreased toward baseline values. We conclude that (1) modest protein ingestion can result in significant transient increases in NH3 in VPA-treated children, (2) significant increases may occur in patients with normal fasting NH3 concentrations, (3) these increases can be significantly attenuated by L-carnitine supplementation, and (4) these changes do not appear to be related to changes in VPA concentration.
authors.affiliation: School of Pharmacy, University of Wisconsin, Madison, USA.
authors.forename: B E
authors.initials: BE
authors.lastname: Gidal
authors.forename: C M
authors.initials: CM
authors.lastname: Inglese
authors.forename: J F
authors.initials: JF
authors.lastname: Meyer
authors.forename: M E
authors.initials: ME
authors.lastname: Pitterle
authors.forename: J
authors.initials: J
authors.lastname: Antonopolous
authors.forename: R S
authors.initials: RS
authors.lastname: Rust
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000641:Ammonia / Q000097:blood*; D000927:Anticonvulsants / Q000009:adverse effects*; D002331:Carnitine / Q000627:therapeutic use*; D002648:Child; D004032:Diet; D004827:Epilepsy / Q000097:blood / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008297:Male; D011446:Prospective Studies; D014635:Valproic Acid / Q000009:adverse effects*
chemical_list: D000927:Anticonvulsants; D014635:Valproic Acid; D000641:Ammonia; D002331:Carnitine