Related Experiment Video

Updated: Jul 9, 2026

A Three-Dimensional Spheroid Model to Investigate the Tumor-Stromal Interaction in Hepatocellular Carcinoma
12:24

A Three-Dimensional Spheroid Model to Investigate the Tumor-Stromal Interaction in Hepatocellular Carcinoma

Published on: September 30, 2021

Imatinib for hepatocellular cancer--focus on pharmacokinetic/pharmacodynamic modelling and liver function

G Treiber1, T Wex, E Schleyer

  • 1Department of Gastroenterology/Hepatology/Infectious Diseases, University Hospital, Magdeburg, Germany. ingtre@uks.eu

Cancer Letters
|December 18, 2007
PubMed

Insights

Imatinib treatment for liver cancer significantly reduced plasma platelet-derived growth factor (PDGF). This reduction was linked to imatinib

Area of Science:

  • Pharmacology
  • Hepatology
  • Oncology

Background:

  • Platelet-derived growth factor (PDGF) is highly expressed in the liver and implicated in cancer.
  • Imatinib is a tyrosine kinase inhibitor with known effects on PDGF.
  • Hepatocellular carcinoma (HCC) is a primary liver cancer with limited treatment options.

Purpose of the Study:

  • To evaluate the pharmacokinetic parameters and safety of imatinib in patients with hepatocellular cancer.
  • To assess the effect of imatinib on plasma PDGF levels in HCC patients.
  • To explore the relationship between imatinib metabolism, liver function, and PDGF inhibition.

Main Methods:

  • Phase I/II clinical trial.
  • Administration of imatinib (400 mg/d for 4 weeks).
  • Measurement of imatinib and N-desmethyl-imatinib plasma concentrations.
  • Assessment of plasma PDGF levels.
  • Correlation analysis between pharmacokinetic parameters, liver function, and PDGF inhibition.

Main Results:

  • Imatinib pharmacokinetic parameters in HCC patients were comparable to those in chronic myeloid leukemia (CML) patients.
  • N-desmethyl-imatinib AUC was influenced by liver function.
  • Short-term imatinib treatment (4 weeks) led to a significant decrease in plasma PDGF.
  • PDGF inhibition was strongly correlated with the AUC of N-desmethyl-imatinib (r=-0.679, p=0.031).

Conclusions:

  • Imatinib demonstrates a pharmacodynamic effect on PDGF inhibition in HCC patients.
  • The metabolism and effects of imatinib in HCC are influenced by liver function.
  • Imatinib represents a potential therapeutic agent for HCC, warranting further investigation into its PDGF-mediated effects.

More Related Videos

A Combined 3D Tissue Engineered In Vitro/In Silico Lung Tumor Model for Predicting Drug Effectiveness in Specific Mutational Backgrounds13:34

A Combined 3D Tissue Engineered In Vitro/In Silico Lung Tumor Model for Predicting Drug Effectiveness in Specific Mutational Backgrounds

Published on: April 6, 2016

A Biomimetic Model for Liver Cancer to Study Tumor-Stroma Interactions in a 3D Environment with Tunable Bio-Physical Properties08:40

A Biomimetic Model for Liver Cancer to Study Tumor-Stroma Interactions in a 3D Environment with Tunable Bio-Physical Properties

Published on: August 7, 2020

Related Concept Videos

Effect of Hepatic Disease on Pharmacokinetics: Pathophysiologic Assessment and Liver Function Test01:22

Effect of Hepatic Disease on Pharmacokinetics: Pathophysiologic Assessment and Liver Function Test

In clinical practice, the direct measurement of hepatic blood flow to evaluate liver function presents significant challenges due to the intricate and specialized nature of the necessary techniques. Consequently, healthcare professionals often rely on empirical estimates derived from thorough patient examinations and liver function tests to gauge liver health. Among the tools at their disposal, the Child–Pugh and MELD scoring systems stand out for their ability to categorize and assess the...
Effect of Hepatic Disease on Pharmacokinetics: Active Drug, Metabolite and Fraction of Metabolized Drug01:14

Effect of Hepatic Disease on Pharmacokinetics: Active Drug, Metabolite and Fraction of Metabolized Drug

In pharmacotherapy, monitoring drug concentrations is paramount, especially for drugs whose therapeutic effects hinge on both the active compound and its metabolite. Hepatic impairment profoundly influences drug potency by altering liver function. If the drug is more potent than its metabolite, impaired liver function amplifies drug activity due to elevated drug concentration levels. Conversely, if the metabolite holds greater potency, diminished liver function diminishes drug activity by...
Effect of Hepatic Disease on Pharmacokinetics: Drug Dosing and Hepatic Blood Flow01:26

Effect of Hepatic Disease on Pharmacokinetics: Drug Dosing and Hepatic Blood Flow

Chronic liver disease significantly impacts drug metabolism due to alterations in hepatic blood flow and enzyme accessibility. This disruption affects the body's pharmacokinetics—the movement and processing of drugs within the system. Key enzymes crucial for metabolizing medications become less accessible, changing how drugs are processed and utilized. Furthermore, liver disease influences the synthesis of plasma proteins, such as albumin and globulins, which play critical roles in drug binding...
Impact of Pharmacokinetic–Pharmacodynamic Models: Regulatory Decisions01:15

Impact of Pharmacokinetic–Pharmacodynamic Models: Regulatory Decisions

PK–PD modeling has significantly influenced FDA regulatory decisions, particularly drug approval, dosage optimization, and labeling. These models integrate pharmacokinetics (PK) and pharmacodynamics (PD) to predict drug behavior and effects, aiding in optimizing dosing regimens and enhancing the probability of clinical trial success.One notable example is Nesiritide (Natrecor®), a recombinant human brain natriuretic peptide for treating acute decompensated congestive heart failure (CHF).
Physiological Pharmacokinetic Models: Incorporating Hepatic Transporter-Mediated Clearance01:07

Physiological Pharmacokinetic Models: Incorporating Hepatic Transporter-Mediated Clearance

Drug transporters are critical in drug absorption, distribution, and excretion processes. They should be included in physiological-based pharmacokinetic (PBPK) models, which help predict human drug disposition. However, predicting this is challenging during drug development, especially when liver transport is involved. However, with a realistic representation of body transport processes, an accurate model may be possible.
A recent model describes pravastatin's hepatobiliary excretion, mediated...
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against specific...