CYP2C19 metabolizes Escitalopram to N-desmethyl escitalopram and escitalopram propionic acid. A recent study investigated the impact of the CYP2C19 phenotype on metabolic ratios of escitalopram in vivo and proposed a biomarker for the CYP2C19 phenotype in patients treated with escitalopram.

The study investigated the Median steady-state serum metabolite/parent drug ratio of N-desmethyl escitalopram and escitalopram propionic acid across CYP2C19 genotype-translated phenotype groups and determined the best suited metabolic ratio for detecting CYP2C19 poor metabolizers (PMs).

The study included 441 patients. It found N-desmethyl escitalopram/escitalopram ratio to be 67% and 44% lower in CYP2C19 PMs and intermediate metabolizers (IMs), respectively, than in normal metabolizers. Furthermore, it found the ability of the ratio to predict CYP2C19 PMs to be 92%. The study detected a metabolic ratio of <0.24 in all PMs, indicating it to be a promising biomarker of reduced CYP2C19 activity. 

Furthermore, it found the escitalopram propionic acid/escitalopram ratio to be 77% and 48% lower in CYP2C19 PMs and IMs, respectively; however, its ability to detect CYP2C19 PMs remained at only 87%.

This study shows that DECT/ECT reflects CYP2C19 activity, and a metabolic ratio of <0.24 strongly predicts the CYP2C19 PM phenotype. This ratio can be used as an alternative to genotyping in personalized dosing of escitalopram and possibly other CYP2C19 substrates. The escitalopram propionic acid/escitalopram ratio also associates with CYP2C19 activity; however, it is inferior to the DECT/ECT at predicting PMs.

Therapeutic Drug Monitoring. 2022;44(6):720-728(9). DOI: https://doi.org/10.1097/FTD.0000000000000991