In Vitro ADME and Preclinical Pharmacokinetics of Ulotaront, a TAAR1/5-HT_1A Receptor Agonist for the Treatment of Schizophrenia.

ABSTRACT:

Purpose

Ulotaront (SEP-363856) is a TAAR1 agonist with 5-HT_1A agonist activity currently in clinical development for the treatment of schizophrenia. The objectives of the current study were to characterize the in vitro ADME properties, preclinical PK, and to evaluate the DDI potential of ulotaront and its major metabolite SEP-383103.

Methods

Solubility, permeability, plasma protein binding, CYP inhibition and induction, transporter inhibition and uptake studies were conducted in vitro. Phenotyping studies were conducted using recombinant human CYPs and FMOs, human liver microsomes and human liver homogenates. Preclinical plasma and brain pharmacokinetics were determined after a single intraperitoneal, intravenous, and oral administration of ulotaront.

Results</

SUBMITTER: Xiao G 

PROVIDER: S-EPMC9160101 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature