Trial reportClinical pharmacokinetics2025
Clinical Exploration and Physiologically Based Modelling of the Impact of Hepatic Impairment on Entrectinib Pharmacokinetics.
Trial report in Clinical pharmacokinetics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04226833 (An Open-Label, One Treatment, Four Group, Parallel Group Study to Investigate the Effect of Impaired Hepatic Function on the Pharmacokinetics of Entrectinib in Volunteers With Different Levels of Hepatic Function), which is not on this map. Cited by 2 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
An Open-Label, One Treatment, Four Group, Parallel Group Study to Investigate the Effect of Impaired Hepatic Function on the Pharmacokinetics of Entrectinib in Volunteers With Different Levels of Hepatic Function
Who cites it
2 citing papers in PubMed.
- Insights into Drug Absorption Impairment Mechanisms in Hepatic Impairment using Physiologically-based Pharmacokinetic Modelling: A Case Study with Nilotinib.The AAPS journal · 2026Article
- Evaluating the Impact of Intestinal Bile Salts on Drug Absorption Using PBPK Modeling: Case Studies With Efavirenz, Cinnarizine, and Posaconazole.CPT: pharmacometrics & systems pharmacology · 2026Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
objectivesThis study investigates the pharmacokinetics (PK) of entrectinib and its metabolite M5 (CYP3A4 substrates) in patients with hepatic impairment (HI) and applies physiologically based pharmacokinetic (PBPK) modelling to understand the observed changes mechanistically.
methodAfter a single oral administration of entrectinib at 100 mg, measured plasma concentrations for entrectinib and M5 in control subjects and HI patients were compared to predictions made with Simcyp
resultsPhysiologically based pharmacokinetic model simulations overestimated the 80% increase in entrectinib area under the plasma concentration curve between 0h to infinity (AUC
conclusionPhysiologically based pharmacokinetic model simulations tended to overestimate the observed moderate changes in entrectinib exposures due to HI. For improved prediction of poorly soluble lipophilic drugs like entrectinib there is a need for PBPK models of HI to account for additional pathophysiological changes such as reduced intestinal BS levels.
trial registrationNCT number: NCT04226833.
Indexed as
Identifiers
39934586What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.