Antidote for Valproic Acid Toxicity: a New Indication for Meropenem Antibiotic.
Status:
Not yet recruiting
Trial end date:
2022-12-01
Target enrollment:
Participant gender:
Summary
Acute Valproic acid (VPA) toxicity is an emergency condition which may commonly present with
central nervous system (CNS) depression(5). In mild poisoning, associated with VPA ingestions
of 200 mg/kg, sedation and lethargy commonly occur(6); while in severe VPA poisoning
associated with ingestions of 400 mg/kg or more, life threatening events are likely to occur
as respiratory depression, metabolic acidosis, encephalopathy, hemodynamic instability, and
cerebral edema which may progress to coma and even death -if not treated promptly. Supportive
care along with early gastric decontamination using activated charcoal (AC) (which may only
be given if patient presented early after ingestion), in addition to intravenous (IV)
administration of Levocarnitine (L-Carnitine) and ensuring adequate airway protection are the
cornerstone of treatment, but there remains no drug listed as a specific antidote for acute
VPA intoxication. Carbapenem antibiotics augment the clearance of VPA through suppressing its
enterohepatic recirculation, as they inhibit the acylpeptide hydrolase enzyme responsible for
the reabsorption of the hydrolyzed valproate back to VPA active molecule. Taking advantage of
this well-established drug-drug interaction between VPA and carbapenems resulting in
significant drop of VPA serum concentration during concomitant use, we propose that
administration of meropenem (member of carbapenems group) will prove effectiveness in
managing VPA toxicity by achieving lower plasma levels of VPA and/or enhanced alertness;
compared with standard care.