Informing Pharmacokinetic Models With Physiological Data: Oral Population Modeling of L-Serine in Humans.

ABSTRACT: To determine how to set optimal oral L-serine (serine) dose levels for a clinical trial, existing literature was surveyed. Data sufficient to set the dose was inadequate, and so an (n = 10) phase I-A calibration trial was performed, administering serine with and without other oral agents. We analyzed the trial and the literature data using pharmacokinetic (PK) modeling and statistical analysis. The therapeutic goal is to modulate specific serine-related metabolic pathways in the liver using the lowest possible dose which gives the desired effect since the upper bound was expected to be limited by toxicity. A standard PK approach, in which a common model structure was selected using a fit to data, yielded a model with a single central compartment corresponding to plasma, clearance fr

SUBMITTER: Bosley JR 

PROVIDER: S-EPMC8156419 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature