The effects of oxcarbazepine and valproate therapies on growth in children with epilepsy.

AIM: This study aimed to evaluate the effects of monotherapy with valproate or oxcarbazepine on the linear growth of children with idiopathic epilepsy. METHODS: Antiepileptic treatment with valproate or oxcarbazepine was initiated in 76 patients. These were evaluated at baseline and at 6 and 18 months after commencement of therapy to determine height standard deviations (height z-scores). Serum ghrelin, insulin-like growth factor-1, and insulin-like growth factor-binding protein-3 levels were measured. RESULTS: In prepubertal patients receiving oxcarbazepine, height z-scores were elevated after 6 and 18 months of therapy (p = 0.008 and p = 0.001, respectively); in pubertal patients, a significant increase was noted at the 18th month of therapy (p = 0.004). In prepubertal patients receiving oxcarbazepine, serum standardized insulin-like growth factor-1 and insulin-like growth factor-binding protein-3 levels were significantly higher at the 18th month of therapy compared with baseline (p = 0.005 and p = 0.004, respectively). In puber-tal patients receiving valproate, serum ghrelin levels were significantly decreased at the 18th month of therapy compared with baseline (p = 0.006). CONCLUSION: Exposure to oxcarbazepine stimulated linear growth in epileptic patients through mechanisms involving the release of insulin-like growth factor-1 and insulin-like growth factor-binding protein-3. In contrast, expo-sure to valproate did not affect linear growth, but did lead to a decrease in serum ghrelin levels.

Analysis of acylcarnitine levels by tandem mass spectrometry in epileptic children receiving valproate and oxcarbazepine.

This prospective study was designed to investigate whether or not monotherapy with sodium valproate (VPA) or oxcarbazepine (OXC) affects plasma levels of fatty acylcarnitine esters in children with epilepsy. A total of 56 children with idiopathic partial or generalised epilepsy were included in the study. Patients were assigned to receive either VPA or OXC monotherapy. Free carnitine (C0) and acylcarnitine profiles of the patients were investigated using tandem mass spectrometry at baseline and at six and 18 months after commencement of therapy. For patients receiving VPA or OXC monotherapy, there were no significant differences in plasma levels of C0, compared with baseline, at six and 18 months (p>0.05). Treatment with VPA for six and 18 months correlated with a significant increase in 3-hydroxy-isovalerylcarnitine (C5-OH) (six months: +23%; 18 months: +73%), and significant decreases in the following acylcarnitines: C6-acylcarnitine (six months: -60%; 18 months: -66%), C14-acylcarnitine (six months: -25%; 18 months: -38%), C16-acylcarnitine (six months: -73%; 18 months: -73%), and C18:1-OH-acylcarnitine (six months: -60%; 18 months: -70%), compared with baseline (p<0.05). In patients receiving OXC monotherapy, on the other hand, plasma concentrations (µmol/L) of acylcarnitines (from C2 to C18:1-OH) fell within the normal reference range. The results of this study indicate that there are significant biochemical changes in acylcarnitines in ambulatory children on VPA monotherapy but these are not clinically significant. OXC monotherapy had no effect on acylcarnitine metabolism in ambulatory children.

Evaluation of bone turnover in epileptic children using oxcarbazepine.

This study evaluated the effects of oxcarbazepine monotherapy on bone turnover in prepubertal and pubertal children. Thirty-four newly diagnosed pediatric patients with normal bone mineral density, serum biochemical markers of bone formation, and hormonal markers participated. Levels of 25-hydroxyvitamin D were significantly decreased after therapy compared with baseline values. Levels of gamma-glutamyl transferase, phosphorus, alkaline phosphatase, osteocalcin, parathyroid hormone, and calcitonin had increased. However, only changes in osteocalcin and gamma-glutamyl transferase levels were statistically significant compared with baseline values. Drug-induced osteopenia was evident in 3 patients with z scores of bone-mineral density less than -2.0, whereas these patients had z scores of less than -1.5 before treatment. Although 18 months of oxcarbazepine treatment exerted slightly adverse effects on bone metabolism, the effect seems insignificant in children with normal bone-mineral density. Although alterations in bone metabolism do not always suffice to explain the decrease in bone-mineral metabolism, we think that patients with osteopenia before the initiation of oxcarbazepine therapy should be followed carefully, especially in long-term treatment.