In vitro assay of pharmacobezoar formation with extended-release divalproex sodium tablets

Abstract

Objective: To assess pharmacobezoar formation in a case of intoxication following the massive ingestion of extended-release divalproex sodium tablets, using an in vitro model conducted in the pharmacy laboratory.

Methods: An in vitro model was created to simulate gastric conditions and evaluate pharmacobezoar formation. Simulated gastric fluid was prepared according to the European Pharmacopeia procedure. The conglomerate's size and pH were measured at 30 min, 1 h, 2 h, 4 h, 8 h, 12 h, and 24 h intervals. Serum valproic acid concentrations were determined at all mentioned time points and then compared with the patient's serum concentrations.

Results: The in vitro model revealed the formation of a solid pharmacobezoar (5 cm x 6 cm) after 2 h (pH = 1.5), which remained stable for 24 h. The peak serum concentration of valproic acid occurred approximately 22 h post-ingestion, reaching 656 μg/mL. The in vitro assay indicated a similar peak concentration around 24 h after the tablets were immersed in the simulated gastric fluid.

Conclusions: The experiment conducted supports the hypothesis of pharmacobezoar formation following excessive ingestion of extended-release divalproex sodium tablets. Understanding which drug formulations can potentially cause pharmacobezoars formation is crucial for toxicological management.

Keywords: Bezoar; Delayed–action preparations; Drug overdose; Preparaciones de acción retardada; Sobreingesta de medicamentos; Toxicidad; Toxicity; Valproic acid; Ácido valproico.