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Possible correlation between ormaplatin biotransformations and neurotoxicity

M Sakata1, S G Chaney, D R Spriggs

  • 1Department of Biochemistry and Biophysics, School of Medicine, University of North Carolina at Chapel Hill 27599-7260, USA.

Oncology Research
|January 1, 1995
PubMed
Summary
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Predicting ormaplatin neurotoxicity may be possible by analyzing plasma biotransformation products. Higher levels of platinum biotransformation products in plasma correlated with neurotoxicity in patients receiving ormaplatin.

Area of Science:

  • Pharmacology
  • Oncology
  • Toxicology

Background:

  • Clinical development of ormaplatin is hindered by unpredictable neurotoxicity.
  • Current methods of predicting toxicity based on patient characteristics, dose, or pharmacokinetics are insufficient.

Purpose of the Study:

  • To compare plasma biotransformations of ormaplatin in patients with and without neurotoxicity.
  • To investigate the utility of analyzing plasma biotransformation products for predicting platinum anticancer agent toxicity.

Main Methods:

  • Detailed comparison of ormaplatin plasma biotransformations in two patients receiving the same dose.
  • Analysis of plasma concentrations of ormaplatin and its major active biotransformation product, dichloro(d,l-trans)1,2-diaminocyclohexanedichloroplatinum(II).

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Main Results:

  • The patient who developed neurotoxicity had higher plasma concentrations of dichloro(d,l-trans)1,2-diaminocyclohexanedichloroplatinum(II) and potentially ormaplatin itself.
  • The patient without neurotoxicity exhibited greater maximum plasma concentration and area under the curve for ultrafilterable platinum.

Conclusions:

  • Analysis of individual plasma biotransformation products may aid in predicting ormaplatin-induced neurotoxicity.
  • Incorporating plasma biotransformation product analysis into future Phase I studies could improve patient safety and treatment outcomes for platinum anticancer agents.