Oxcarbazepine, a keto-analogue of
carbamazepine, was recently approved in the United States for the treatment of
seizures of partial onset. Some patients treated with
oxcarbazepine showed the development of
hyponatremia, which in most instances was asymptomatic. Understanding the mechanisms by which
oxcarbazepine can lead to a reduction of serum
sodium levels could have therapeutic implications for the few patients in whom symptomatic
hyponatremia develops. In this study, we evaluated
sodium and water handling in patients with
epilepsy and in healthy subjects titrated over 3 weeks to a maximum daily
oxcarbazepine dose of 2,400mg. All subjects were evaluated in a hospital setting after an overnight fast and after an acute water-load test performed before
oxcarbazepine exposure and after maintenance on the medication for 3 weeks. Before
oxcarbazepine exposure, the percentage of water load excreted was normal as both groups excreted more than 80% of the administered water load. After the intake of
oxcarbazepine, the water load resulted in a reduction of the serum
sodium and free water clearance without a concomitant increase in the
arginine vasopressin serum levels. Most subjects in both groups failed to excrete 80% or more of the water load, suggesting that the effect of
oxcarbazepine is physiological. We found that, after the water load, serum
sodium and free water clearance were diminished in both groups without a concomitant increase in the
arginine vasopressin serum levels. These findings indicate that
oxcarbazepine-induced
hyponatremia is not attributable to the syndrome of inappropriate secretion of
antidiuretic hormone. Possible mechanisms include a direct effect of
oxcarbazepine on the renal collecting tubules or an enhancement of their responsiveness to circulating
antidiuretic hormone.