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Related Experiment Videos

Interindividual variabilities in haloperidol interconversion and the reduced haloperidol/haloperidol ratio.

Y W Lam1, W H Chang, M W Jann

  • 1Department of Pharmacology, University of Texas Health Science Center, San Antonio 78284-6220.

Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology
|August 1, 1992
PubMed
Summary

This study investigated haloperidol metabolism in Chinese schizophrenics, revealing significant interindividual variability in N-dealkylation and reduction pathways. These variations impact how the body processes haloperidol and its metabolite, reduced haloperidol.

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Area of Science:

  • Pharmacology
  • Clinical Pharmacy
  • Psychiatry

Background:

  • Haloperidol is an antipsychotic drug metabolized via N-dealkylation and reduction.
  • Reduced haloperidol can be interconverted back to haloperidol through oxidation.

Purpose of the Study:

  • To determine the metabolic clearance of haloperidol and reduced haloperidol in Chinese schizophrenic patients.
  • To investigate interindividual variability in haloperidol metabolism and its relationship to N-dealkylation and reduction pathways.

Main Methods:

  • A randomized crossover study administering single oral doses of haloperidol and reduced haloperidol to seven Chinese schizophrenics.
  • Determination of metabolic clearance values for different pathways.
  • Assessment of reduced haloperidol to haloperidol concentration ratio after 4 weeks of twice-daily haloperidol therapy.

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Main Results:

  • Significant interindividual variability, up to 10-fold, was observed in oxidation and reduction capacities.
  • Variability in elimination rates for reduced haloperidol (0.37 +/- 0.20 L/hr/kg) and N-dealkylation (0.74 +/- 0.36 L/hr/kg) was noted.
  • The reduced haloperidol to haloperidol ratio (0.40 +/- 0.16) after therapy correlated with individual variability in interconversion and N-dealkylation.

Conclusions:

  • Interindividual differences in haloperidol metabolism, particularly N-dealkylation and reduction, are substantial in Chinese schizophrenic patients.
  • These metabolic variations influence the interconversion between haloperidol and reduced haloperidol, affecting drug disposition.