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Effects of Valproic Acid, Carbamazepine, and Phenobarbitone on the Fatty Acid Composition of Erythrocyte Membranes in Children

2003; Wiley; Volume: 44; Issue: 5 Linguagem: Inglês

10.1046/j.1528-1157.2003.09802.x

1528-1167

Stephan A. König, Julia Knolle, Steffen Friedewald, W. Koelfen, Elke Longin, Tamara Lenz, D Hannak,

Drug Transport and Resistance Mechanisms

Summary: Purpose: To investigate a possible relation between antiepileptic drugs (AEDs) and the fatty acid composition of membranes. Methods: Fatty acid (FA) composition of erythrocytes was studied in children with epilepsy receiving AED monotherapy. Children taking valproate (VPA, n = 28), carbamazepine (CBZ, n = 17), or phenobarbitone (PB, n = 14) were compared with healthy controls (n = 25). FAs were measured by capillary‐gas chromatography (GC‐FID). Results: Significant changes (p < 0.05) in the FA composition of membranes were found. In children treated with VPA, C13:0 was decreased (8.2 ± 2% vs. 10.7 ± 4% in controls) and C14:0 increased (1.4 ± 0.5% vs.1 ± 0.5% in controls). C17:0 again was reduced (9.9 ± 4% vs. 13.2 ± 6% in controls), whereas the long‐chained acids were enhanced: C18:2n‐6 (6 ± 2.4% vs. 3.9 ± 2.5% in controls), and C20:4n‐6 (1.9 ± 1.7% vs. 1.4 ± 0.5% in controls). The nonidentified FAs also increased with VPA therapy: 2.5 ± 0.8% versus 1.7 ± 0.9% in controls. Children treated with CBZ showed only minimal changes of FA composition: C13:0 was decreased compared with controls (8 ± 2% vs. 10.7 ± 4%). No changes were seen in patients taking PB. The mean corpuscular volume (MCV) showed important differences between the study groups: MCV was 84.7 ± 6.0 fl during VPA therapy (p < 0.001) and 85.7 ± 4.1 fl with CBZ (p < 0.001). During PB, the MCV increased to 82.87 ± 3.29 fl compared with controls (78.73 ± 4.92 fl; p < 0.01). Conclusions: VPA therapy is associated with changes of the FA composition of membranes, which is not the case with PB therapy. The implications of this finding remain to be established.