Adaptation of hepatic ammonia metabolism after chronic valproate administration in epileptics treated with phenytoin.
The effects of phenytoin (PHT) on the modifications of ammonia (NH+4) metabolism caused by sodium valproate (VPA) are here studied in order to identify the drug combinations susceptible of evoking stuporous states in epileptics, a rare condition attributed to a hyperammonemic encephalopathy induced by VPA. During chronic treatment with PHT or VPA-PHT, the acute injection of VPA increases the kidney's output of NH+4. During chronic PHT treatments, the acute injection of VPA modifies the liver's NH+4 metabolism and the arterial hyperammonemia is high (mean = 90 mumol/l). During chronic VPA-PHT treatments, the acute injection of VPA does not affect the hepatic NH+4 metabolism, suggesting that adaptation occurs, and the arterial hyperammonemia is moderate (mean = 60 numol/l). Disturbances of the hepatic adaptive mechanisms may explain certain complications observed during multiple-drug regimens.
D000222:Adaptation, Physiological; D000328:Adult; D000641:Ammonia / Q000097:blood / Q000378:metabolism*; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D004827:Epilepsy / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008875:Middle Aged; D010672:Phenytoin / Q000494:pharmacology* / Q000627:therapeutic use; D014635:Valproic Acid / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use
D014635:Valproic Acid; D010672:Phenytoin; D000641:Ammonia