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Decrease in penbutolol protein binding as a consequence of treatment with some alkylating agents

C Aguirre1, J M Rodríguez-Sasiain, R Calvo

  • 1Pharmacology Department, Basque Country University School of Medicine, Leioa, Spain.

Cancer Chemotherapy and Pharmacology
|January 1, 1994
PubMed
Summary
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Alkylating agents like carmustine and mechlorethamine significantly increase the free fraction of penbutolol in serum by altering protein binding. This interaction is crucial for cancer patients receiving combined therapies.

Area of Science:

  • Pharmacology
  • Biochemistry
  • Oncology

Background:

  • Penbutolol is a basic drug primarily bound to alpha 1-acid glycoprotein (AAG) in serum.
  • Alkylating agents are used in cancer treatment and can affect biological molecules.

Purpose of the Study:

  • To investigate the in vitro effect of carmustine (BCNU) and mechlorethamine on penbutolol's protein binding in serum.
  • To understand potential drug interactions in cancer patients undergoing combined therapies.

Main Methods:

  • In vitro treatment of human serum with carmustine (BCNU) and mechlorethamine.
  • Measurement of the free fraction of penbutolol using established methods.
  • Incubation time-course and dialysis experiments were performed.

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Main Results:

  • BCNU and mechlorethamine significantly increased the free fraction of penbutolol (P < 0.001).
  • BCNU caused a sustained increase in penbutolol's free fraction over 2 hours.
  • Dialysis did not reverse the increased free fraction of penbutolol after carmustine treatment.

Conclusions:

  • In vitro treatment with alkylating agents alters serum protein binding capacity.
  • This alteration can significantly increase the free fraction of basic drugs like penbutolol.
  • Clinical consideration is needed for concurrent administration of alkylating agents and basic drugs in cancer patients.