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Hepatotoxicity and metabolism of trabectedin: a literature review

J H Beumer1, J H M Schellens, J H Beijnen

  • 1Department of Pharmacy and Pharmacology, Slotervaart Hospital, The Netherlands Cancer Institute, Louwesweg 6, 1066 EC Amsterdam, The Netherlands. apjbe@slz.nl

Pharmacological Research
|March 8, 2005
PubMed

Insights

Trabectedin

Area of Science:

  • Pharmacology
  • Hepatotoxicity
  • Drug Metabolism

Background:

  • Trabectedin is an anticancer drug with observed hepatotoxicity and reversible increases in liver enzymes in patients.
  • Preclinical studies suggested trabectedin metabolism contributes to its pharmacological effects, including liver toxicity.

Purpose of the Study:

  • To review literature on trabectedin metabolism and its role in hepatotoxicity and liver enzyme elevation.
  • To compare metabolic profiles and hepatotoxicity across species, focusing on relevance to human response.

Main Methods:

  • Literature review of studies on trabectedin metabolism, hepatotoxicity, and liver enzyme changes.
  • Comparative analysis of preclinical (rat) and clinical (human, monkey) data.

Main Results:

  • Trabectedin's metabolic profile correlates with the reversible nature of its hepatotoxicity.
  • Rats exhibit different metabolic profiles and hepatotoxicity reversibility compared to humans.
  • Humans and monkeys show similar metabolic profiles and reversible hepatotoxicity.

Conclusions:

  • Trabectedin exhibits predictable and reversible hepatotoxic effects.
  • Monitoring liver enzymes is crucial for safe clinical use of trabectedin.
  • Further research is needed to elucidate the mechanism of trabectedin-induced hepatotoxicity.

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