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Updated: Sep 3, 2025

Measurement of Fatty Acid β-Oxidation in a Suspension of Freshly Isolated Mouse Hepatocytes
Published on: September 9, 2021
Population Pharmacokinetics of Heptanoate in Healthy Subjects and Patients With Long-Chain Fatty Acid Oxidation
Sun Ku Lee1, Nathalie H Gosselin2, Claudia Jomphe2
1Ultragenyx Pharmaceutical Inc., Novato, California, USA.
Abstract:
Triheptanoin is an odd-carbon, medium-chain triglyceride consisting of three fatty acids with seven carbons each on a glycerol backbone, indicated for the treatment of adult and pediatric patients with long-chain fatty acid oxidation disorders (LC-FAOD). A total of 562 plasma concentrations of heptanoate, the most abundant and pharmacologically active metabolite of triheptanoin, from 13 healthy adult subjects and 30 adult and pediatric subjects with LC-FAOD were included in the population pharmacokinetic (PK) analyses. Multiple peaks of heptanoate observed in several subjects were characterized by dual first-order absorption with a lag time in the second absorption compartment. The disposition of heptanoate in human plasma was adequately described by one-compartmental distribution with a linear elimination. The apparent clearance (CL/F) and apparent volume of distribution were allometrically scaled with body weight to describe PK data across a wide range of age groups in subjects with LC-FAOD. The typical CL/F in adult subjects with LC-FAOD was ≈19% lower than that in healthy subjects. Model-estimated elimination half-life for LC-FAOD patients was ∼1.7 hours, supporting a recommended dosing frequency of ≥4 times per day. Covariate analyses indicate that age, race, and sex did not lead to clinically meaningful changes in the exposure of heptanoate.
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