Antidote for Valproic Acid Toxicity: a New Indication for Meropenem Antibiotic.

• Status: Not yet recruiting
• Trial end date: 2022-12-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Mabaret Al-Asafara Hospitals
• Treatments: Meropenem

Criteria

Inclusion Criteria:

• Patients with VPA toxicity will be included if aged 18 years or more. The patient himself/herself should provide informed consent; a family member may take place only if there is an altered mentation that may hinder such procedure.

Exclusion Criteria:

• Patients will be excluded if presenting one hour following VPA ingestion and were administered AC for gastric decontamination, as it may decrease VPA bioavailability.