L-Arginine in the treatment of valproate overdose - five clinical cases.
Valproic acid and its metabolites - particularly valproyl-CoA - are inhibitors of the enzyme N-acetylglutamate synthetase. The amino acid l-arginine can stimulate N-acetylglutamate synthetase activity and could be potentially used therapeutically to correct hyperammonemia caused by valproate therapy or overdose. Severely valproic-acid-poisoned patients are usually treated with l-carnitine or hemodialysis in order to decrease hyperammonemia. We herein report of five cases, in which l-arginine was administered.



Observational study on five cases. Patients with hyperammonemia (i.e., ammonia 80 > μg/dL) and symptoms consistent with valproate overdose (i.e., drowsiness, coma) were selected for treatment with l-arginine. Data was collected retrospectively.



l-Arginine decreased ammonia levels in a close temporal relation (case I ammonia in EDTA-plasma [μg/dL] decreased from 381 to 39; case II from 281 to 50; case III from 669 to 74; case IV from 447 to 56; case V from 202 to 60). In cases I and II, hemodialysis was performed and l-carnitine was given before the administration of l-arginine. In case III, hemodialysis was performed after the administration of l-arginine was already started. In cases IV and V, treatment with l-arginine was the sole measure to decrease ammonia levels in plasma.



The results suggest that l-arginine may be beneficial in selected cases of valproate overdose complicated by hyperammonemia. l-Arginine could extend our conventional treatment options for valproic acid overdose.
a Department of Clinical Toxicology , Klinikum Rechts der Isar, Technical University of Munich (TUM) , Munich , Germany.
Verena
V
Schrettl
a Department of Clinical Toxicology , Klinikum Rechts der Isar, Technical University of Munich (TUM) , Munich , Germany.
Norbert
N
Felgenhauer
a Department of Clinical Toxicology , Klinikum Rechts der Isar, Technical University of Munich (TUM) , Munich , Germany.
Christian
C
Rabe
b Laboratory of Clinical Biochemistry and Metabolism , Center for Pediatrics and Adolescent Medicine Freiburg, University Freiburg , Freiburg , Germany.
Malkanthi
M
Fernando
a Department of Clinical Toxicology , Klinikum Rechts der Isar, Technical University of Munich (TUM) , Munich , Germany.
Florian
F
Eyer
D000214:Acyl Coenzyme A / Q000097:blood / Q000506:poisoning; D000328:Adult; D051046:Amino-Acid N-Acetyltransferase / Q000037:antagonists & inhibitors / Q000097:blood; D000641:Ammonia / Q000097:blood; D001120:Arginine / Q000627:therapeutic use*; D002331:Carnitine / Q000627:therapeutic use; D003128:Coma / Q000139:chemically induced / Q000188:drug therapy; D062787:Drug Overdose / Q000097:blood / Q000188:drug therapy*; D005260:Female; D006801:Humans; D022124:Hyperammonemia / Q000097:blood / Q000188:drug therapy; D008297:Male; D006435:Renal Dialysis; D014635:Valproic Acid / Q000097:blood / Q000506:poisoning*
D000214:Acyl Coenzyme A; C045335:valproyl-coenzyme A; D014635:Valproic Acid; D000641:Ammonia; D001120:Arginine; D051046:Amino-Acid N-Acetyltransferase; D002331:Carnitine
N-acetylglutamate synthetase; hyperammonemia; l-Arginine; valproic acid