Effects of oxcarbazepine on sodium concentration and water handling.
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.
New Jersey Comprehensive Epilepsy Center, University of Medicine and Dentistry of New Jersey, New Brunswick, NJ 08901, USA. sachderc@umdnj.edu
Rajesh C
RC
Sachdeo
Alan
A
Wasserstein
Peter J
PJ
Mesenbrink
Joseph
J
D'Souza
D000293:Adolescent; D000328:Adult; D000927:Anticonvulsants / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D001127:Arginine Vasopressin / Q000097:blood; D001834:Body Water / Q000378:metabolism*; D002220:Carbamazepine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004827:Epilepsy / Q000097:blood / Q000652:urine; D005260:Female; D006801:Humans; D007010:Hyponatremia / Q000097:blood / Q000139:chemically induced / Q000652:urine; D008297:Male; D008875:Middle Aged; D000078330:Oxcarbazepine; D012964:Sodium / Q000097:blood* / Q000652:urine*; D014554:Urination / Q000187:drug effects / Q000502:physiology; D014556:Urine; D014868:Water Deprivation / Q000502:physiology
D000927:Anticonvulsants; D001127:Arginine Vasopressin; D002220:Carbamazepine; D012964:Sodium; D000078330:Oxcarbazepine