Document Type

Article

Publication Date

9-1-2021

Publication Title

International Journal of Bipolar Disorders

Volume

9

First page number:

1

Last page number:

7

Abstract

Although valproic acid (VPA) induces the metabolism of multiple other drugs, the clinical reports of VPA autoinduction are rare. A comprehensive literature search yielded only one published case series, which provided the rationale to conduct a review of the published cases along with a new case of VPA autoinduction. Although there may be myriad of reasons for lack of published cases of VPA autoinduction, potential underreporting may be one of the core reasons. Lack of understanding into the highly complex metabolism of VPA may also make it difficult to recognize and report VPA autoinduction. However, it is important to mention that in addition to autoinduction increased elimination of VPA may be mediated by several pharmacokinetic (PK) factors, such as drug interactions, genetic polymorphisms of metabolic enzymes, and protein displacement reactions. As VPA is metabolized by multiple metabolic pathways, the risk for drug interactions is relatively high. There is also a growing evidence for high genetic inducibility of some enzymes involved in VPA metabolism. Protein displacement reactions with VPA increase the biologically active and readily metabolizable free fraction and pose a diagnostic challenge as they are usually not requested by most clinicians. Thus, monitoring of free fraction with total VPA levels may prevent clinically serious outcomes and optimize VPA treatment in clinically challenging patients. This case-based review compares the clinical data from three published cases and a new case of VPA autoinduction to enhance clinicians' awareness of this relatively rare but clinically relevant phenomenon along with a discussion of potential underlying mechanisms.

Keywords

Valproic; Acid; Autoinduction; Case-based; Review

Disciplines

Pharmaceutics and Drug Design | Psychiatry

File Format

pdf

File Size

707 KB

Language

English

Rights

IN COPYRIGHT. For more information about this rights statement, please visit http://rightsstatements.org/vocab/InC/1.0/

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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