Valproate can cause carnitine deficiency--abstract

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1: Int J Clin Lab Res 1999;29(1):36-40 Related Articles, Books,

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Carnitine deficiency and hyperammonemia in children receiving

valproic acid with and without other anticonvulsant drugs.

Verrotti A, Greco R, Morgese G, Chiarelli F.

Department of Pediatrics, University of Chieti, Italy.

Plasma ammonia and total and free carnitine were measured in 84

children requiring anticonvulsant drugs: 32 patients (group A) on

valproic acid alone, 28 children (group on polytherapy including

valproic acid, and 24 patients (group C) on polytherapy without

valproic acid. The other anticonvulsant drugs used in groups B and C

were carbamazepine and phenobarbital. Plasma ammonia concentrations

were elevated in both group A and B compared with controls. Group B

patients showed significantly higher hyperammonemia than group A

(59.9 +/- 16.3 micrograms/dl vs. 36.7 +/- 12.4 micrograms/dl; P <

0.05). Group C patients had plasma ammonia levels similar to those of

controls (31.1 +/- 14.7 micrograms/dl vs. 29.7 +/- 12.1

micrograms/dl; NS). In both group A and group B patients, plasma

ammonia levels were correlated with the valproic acid dosage (r =

0.32, P < 0.01) and with serum concentrations of valproic acid (r =

0.41, P < 0.001). Moreover, a significant correlation between plasma

ammonia and duration of valproic acid therapy was found in the

patients as a whole (r = 0.31, P < 0.01). Plasma total and free

carnitine concentrations were significantly reduced in groups A and B

(total carnitine 36.9 +/- 6.9 mumol/l vs. 32.9 +/- 9.7 mumol/l; free

carnitine 28.9 +/- 5.1 mumol/l vs. 25.7 +/- 4.3 mumol/l,

respectively) compared with group C patients who did not receive

valproic acid and in whom values were similar to controls (total

carnitine 46.1 +/- 9.0 mumol/l vs. 47.7 +/- 10.1 mumol/l; free

carnitine 40.1 +/- 7.1 mumol/l vs. 42.9 +/- 8.0 mumol/l,

respectively). Twenty-eight patients (18 of group A and 10 of group

were re-evaluated and showed a complete normalization of plasma

ammonia, and total and free carnitine levels which were similar to

controls. Our data suggest that hyperammonemia is an important

problem in patients receiving valproic acid, particularly in

association with other anticonvulsant drugs. This increase of plasma

ammonia and the concomitant reduction of carnitine seem to be

transient and completely reversible.

PMID: 10356662 [PubMed - indexed for MEDLINE]

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