Related Experiment Video

Updated: Sep 10, 2026

Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs
10:44

Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs

Published on: May 15, 2019

Etoposide pharmacology

K R Hande1

  • 1Vanderbilt University School of Medicine, Nashville, TN.

Seminars in Oncology
|December 1, 1992
PubMed

Insights

Etoposide is an effective anticancer drug that works by breaking cancer cell DNA. Research is exploring how to optimize its dosing by studying its pharmacokinetics and patient variability.

Area of Science:

  • Pharmacology
  • Oncology
  • Molecular Biology

Background:

  • Etoposide, a podophyllotoxin derivative, exhibits significant antitumor activity against various human cancers, including lymphomas, germ cell tumors, and small cell lung cancer.
  • Its mechanism of action involves inducing DNA strand breaks via a complex with DNA and topoisomerase II.
  • Etoposide is characterized by a volume of distribution of 5-17 L/m2 and high plasma protein binding (94% bound, 6% free fraction).

Purpose of the Study:

  • To review the pharmacokinetic properties of etoposide, including its metabolism, distribution, and excretion.
  • To discuss mechanisms of etoposide resistance, particularly those involving membrane transport.
  • To highlight the variability in etoposide pharmacokinetics and explore correlations between plasma concentrations and toxicity for dose optimization.

Main Methods:

  • Literature review of etoposide's pharmacological and pharmacokinetic properties.
  • Analysis of studies investigating etoposide metabolism and excretion pathways (renal and biliary).
  • Examination of research on etoposide resistance mechanisms and pharmacokinetic variability in patients.

Main Results:

  • Etoposide undergoes metabolism, with several metabolites identified or proposed.
  • Acquired resistance to etoposide can occur through alterations in membrane transport mechanisms.
  • Significant intrapatient variability in pharmacokinetic parameters is observed for both intravenous and oral administration.
  • Renal excretion accounts for 30-40% of unchanged intravenous etoposide; biliary excretion is minimal.
  • Oral etoposide bioavailability averages 50% but shows considerable inter- and intrapatient variability, decreasing with higher doses.

Conclusions:

  • Understanding etoposide's pharmacokinetics, metabolism, and resistance mechanisms is crucial for effective cancer treatment.
  • The significant variability in etoposide bioavailability and disposition necessitates careful dosing and monitoring.
  • Correlating etoposide plasma concentrations with toxicity, such as myelosuppression, may lead to optimized therapeutic strategies and improved patient outcomes.

More Related Videos

Detection of DNA Double-Stranded Breaks in Mouse Oocytes07:46

Detection of DNA Double-Stranded Breaks in Mouse Oocytes

Published on: June 23, 2023

MEDUSA for Identifying Death Regulatory Genes in Chemo-genetic Profiling Data07:17

MEDUSA for Identifying Death Regulatory Genes in Chemo-genetic Profiling Data

Published on: February 7, 2025

Related Concept Videos

Antiepileptic Drugs: Potassium Channel Activators01:20

Antiepileptic Drugs: Potassium Channel Activators

Ezocgabine or retigabine, an antiepileptic drug of remarkable efficacy, has revolutionized the management of seizures. It is a potassium channel activator, explicitly targeting the family of Q subtype potassium channels. It enhances the transmembrane potassium currents, regulating neuronal excitability. This action stabilizes the resting membrane potential, a pivotal factor in mitigating the hyperexcitability that characterizes epilepsy.
Ezogabine has gained approval as an adjunctive treatment...
Pharmacodynamics: Overview and Principles01:21

Pharmacodynamics: Overview and Principles

Pharmacodynamics is a scientific field that delves into drugs' intricate biochemical, cellular, and physiological effects on the human body. The study of pharmacodynamics helps us understand how drugs interact with the body and elicit various responses.
Most drugs' effects result from their interactions with drug receptors or targets within the body. These interactions trigger specific responses at the cellular or systemic level. Drug receptors can be found on the surfaces of cells or within...
Pharmacokinetics in Pediatric Patients: Drug Metabolism01:24

Pharmacokinetics in Pediatric Patients: Drug Metabolism

In pediatric care, understanding the nuances of hepatic drug metabolism is crucial, as it significantly differs from that of adults. This divergence is primarily due to the developmental stage of drug-metabolizing enzymes, which affects how medications are processed in the body. In neonates, for instance, the activity of Phase I enzymes—critical for the initial breakdown of drugs—is markedly reduced, functioning at just 20–40% of the levels seen in adults. This reduction poses a challenge in...
Pharmacokinetics in Pediatric Patients: Drug Excretion01:26

Pharmacokinetics in Pediatric Patients: Drug Excretion

In pediatric medicine, understanding the renal function and drug elimination nuances is crucial for administering safe and effective treatments. Newborns, in particular, display markedly slower renal functions than adults, profoundly affecting how drugs are cleared from their bodies. This slower drug clearance requires clinicians to extend the dosing intervals for many medications to prevent drug accumulation and toxicity while ensuring therapeutic efficacy.One key area where these adjustments...
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).
Pharmaceutical Poisoning: Treatment Strategies01:26

Pharmaceutical Poisoning: Treatment Strategies

Treatment strategies for poisoning are a critical aspect of emergency medicine, focusing on preventing the absorption of toxins and enhancing their elimination. When a poisoning incident occurs, the first response is to halt exposure and decontaminate the patient, particularly through gastrointestinal (GI) methods if the poison was ingested.Gastrointestinal Decontamination Techniques:Activated charcoal is the cornerstone of GI decontamination. It works through adsorption, binding the toxin to...