Related Experiment Video

Updated: May 8, 2025

An Intestine/Liver Microphysiological System for Drug Pharmacokinetic and Toxicological Assessment
08:59

An Intestine/Liver Microphysiological System for Drug Pharmacokinetic and Toxicological Assessment

Published on: December 3, 2020

7.7K

Pharmacokinetics and Safety of Navitoclax in Hepatic Impairment

Maulik Patel1, Jalaja Potluri2, Thomas Marbury3

  • 1Clinical Pharmacology, AbbVie Inc, South San Francisco, CA, USA.

Clinical Pharmacokinetics
|March 27, 2025
PubMed
Abstract

Insights

This study found that navitoclax pharmacokinetics and safety were similar in patients with mild to moderate liver impairment compared to those with normal liver function. No dose adjustment is needed for these patients with myelofibrosis.

Area of Science:

  • Pharmacology
  • Hepatology
  • Oncology

Background:

  • Navitoclax is an oral inhibitor of antiapoptotic B-cell lymphoma-2 (Bcl-2) family proteins, investigated for myelofibrosis (MF).
  • Hepatic metabolism of navitoclax necessitates understanding its pharmacokinetics in liver impairment.

Purpose of the Study:

  • To evaluate the pharmacokinetics (PK) and safety of navitoclax in participants with hepatic impairment.
  • To determine if dose adjustments are necessary for patients with MF and liver dysfunction.

Main Methods:

  • A Phase 1 study assessed single-dose navitoclax (50 mg) pharmacokinetics and safety.
  • Participants included those with mild (N=6), moderate (N=6), or severe (N=1) hepatic impairment and matched controls (N=7), classified by Child-Pugh score.
  • Demographics were matched for age, weight, and race.

Main Results:

  • Navitoclax Cmax, AUC0-∞, and t1/2 were comparable in mild and moderate hepatic impairment versus normal liver function.
  • Changes in Cmax and AUC0-∞ were within 25% for mild and moderate impairment.
  • Adverse events were infrequent (10%), primarily grade 1 nausea and diarrhea.

Conclusions:

  • Navitoclax demonstrated a comparable pharmacokinetic profile and safety in patients with mild to moderate hepatic impairment.
  • No new safety concerns were identified.
  • No dose adjustment of navitoclax is required for patients with myelofibrosis and mild or moderate hepatic impairment.

More Related Videos

Human Liver Microphysiological System for Assessing Drug-Induced Liver Toxicity In Vitro11:06

Human Liver Microphysiological System for Assessing Drug-Induced Liver Toxicity In Vitro

Published on: January 31, 2022

4.2K
Optimized LC-MS/MS Method for the High-throughput Analysis of Clinical Samples of Ivacaftor, Its Major Metabolites, and Lumacaftor in Biological Fluids of Cystic Fibrosis Patients06:14

Optimized LC-MS/MS Method for the High-throughput Analysis of Clinical Samples of Ivacaftor, Its Major Metabolites, and Lumacaftor in Biological Fluids of Cystic Fibrosis Patients

Published on: October 15, 2017

8.2K

Related Concept Videos

Antiarrhythmic Drugs: Class I Agents as Sodium Channel Blockers01:22

Antiarrhythmic Drugs: Class I Agents as Sodium Channel Blockers

Class I antiarrhythmic drugs are used to treat various types of arrhythmias or irregular heart rhythms. These drugs block the sodium (Na+) channels in the cardiac cells, thereby affecting the movement of electrical impulses across the heart. Class I antiarrhythmic drugs are divided into three subgroups: Class IA, Class IB, and Class IC, each with distinct mechanisms of action and effects on the heart.
Class 1A Antiarrhythmic Drugs: These drugs work by moderately blocking sodium channels,...
1.0K
Hepatic Drug Clearance: Effect of Protein Binding01:09

Hepatic Drug Clearance: Effect of Protein Binding

Hepatic clearance is influenced by protein binding based on the drug's extraction ratio. Drugs with high extraction ratios are considered flow-limited and remain unaffected by protein binding during hepatic clearance. On the other hand, drugs with low extraction ratios may be impacted by plasma protein binding, although the extent of this influence depends on the fraction of the drug bound.
For low-extraction-ratio drugs that are less than 80% protein-bound, minor changes in protein binding...
97
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,...
13
Factors Affecting Drug Response: Overview01:21

Factors Affecting Drug Response: Overview

When it comes to infants and young children, they are typically administered smaller doses of medication in comparison to adults. This is primarily because their organ functions still need to fully develop, meaning their bodies are not as efficient at metabolizing or eliminating drugs. Additionally, their blood-brain barrier is more permeable than in adults. As a result, high concentrations of drugs can easily penetrate the central nervous system (CNS), potentially leading to neurological...
1.6K
Nonlinear Pharmacokinetics: Dependence of Elimination Half-Life and Dose Clearance01:23

Nonlinear Pharmacokinetics: Dependence of Elimination Half-Life and Dose Clearance

The elimination half-life and drug clearance of drugs following nonlinear kinetics can vary with dosage. The Michaelis-Menten parameters and drug concentration influence these factors. As the dose increases, the elimination half-life tends to lengthen, resulting in a reduction in clearance and a disproportionately larger area under the curve. The total clearance can be derived from the Michaelis-Menten equation for drugs following a one-compartment model.
A study on guinea pigs examined the...
34
Hepatic Drug Clearance: Role of Transporters01:14

Hepatic Drug Clearance: Role of Transporters

In the liver and bile canaliculi, influx and efflux transporters modification can influence intrinsic clearance. Transporters play a significant role in moving drugs within liver cells. Elaborate models, such as the Biopharmaceutical Classification System (BCS), are essential to relate transporters to drug disposition. This system categorizes drugs into four classes based on solubility and permeability, providing insights into elimination routes and the effects of transporters following oral...
21