CYP2C19-Guided Escitalopram and Sertraline Dosing in Pediatric Patients: A Pharmacokinetic Modeling Study

Journal of Child and Adolescent Psychopharmacology
Jeffrey R StrawnLaura B Ramsey

Abstract

Objective: Cytochrome P4502C19 (CYP2C19) is a highly polymorphic gene that encodes an enzyme that metabolizes escitalopram and sertraline, two selective serotonin reuptake inhibitors (SSRIs) that are FDA approved for pediatric use and commonly used to treat anxiety and depressive disorders in youth. Using pharmacokinetic (PK) models in adolescents, we sought to (1) model SSRI dosing across CYP2C19 phenotypes to compare SSRI exposure (area under curve, AUC) and maximum concentration (Cmax), (2) evaluate the impact of b.i.d. dosing (in rapid metabolizers [RM] and ultrarapid metabolizers [UM]) on SSRI exposure and Cmax, and (3) determine pharmacogenomically-informed dosing strategies to provide similar exposure across CYP2C19 phenotypes in adolescents. Methods: Using PK parameters in CYP2C19 phenotype groups and previously reported pediatric PK data for escitalopram and sertraline, we modeled exposure (AUC0-24) and Cmax and determined CYP2C19-guided dosing strategies. Results: Compared with normal CYP2C19 metabolizers treated with either escitalopram or sertraline, Cmax and AUC0-24 were higher in slower metabolizers and lower in patients with increased CYP2C19 activity, although the magnitude of these differences was more pro...Continue Reading

References

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Citations

Feb 9, 2020·Journal of Child Psychology and Psychiatry, and Allied Disciplines·Jeffrey R Strawn, Paul E Croarkin
May 9, 2019·Journal of Child and Adolescent Psychopharmacology·Ethan A PoweleitLaura B Ramsey
Mar 21, 2020·Therapeutic Drug Monitoring·Stefanie FeketeManfred Gerlach
Apr 22, 2020·Journal of Child and Adolescent Psychopharmacology·Jeffrey R StrawnPaul E Croarkin
Oct 14, 2020·Clinical and Translational Science·Timothy A RobertsStephani L Stancil
Nov 10, 2020·Clinical and Translational Science·Karla Claudio-CamposCarol A Mathews
Aug 30, 2020·Journal of the American Academy of Child and Adolescent Psychiatry·Laura B RamseyJeffrey R Strawn
May 2, 2021·Expert Opinion on Drug Metabolism & Toxicology·Abdullah Alkattan, Eman Alsalameen
Jun 7, 2021·Journal of the American Academy of Child and Adolescent Psychiatry·Adelaide S Robb, UNKNOWN AACAP Psychopharmacology Committee
Jul 3, 2021·Journal of Personalized Medicine·Samuel E VaughnLaura B Ramsey
Jan 28, 2022·Pharmacogenomics·Jacob T BrownJeffrey R Bishop

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