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Related Experiment Videos

Interaction between allopurinol and pyrazinamide.

C Lacroix1, C Guyonnaud, M Chaou

  • 1Department of Pharmacokinetics, Centre Hospitalier Général, Le Harve, France.

The European Respiratory Journal
|October 1, 1988
PubMed
Summary
This summary is machine-generated.

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Allopurinol does not improve hyperuricemia caused by pyrazinamide (PZA) treatment for tuberculosis. Instead, it increases pyrazinoic acid, worsening kidney urate secretion inhibition.

Area of Science:

  • Pharmacology
  • Nephrology
  • Infectious Diseases

Background:

  • Pyrazinamide (PZA) is a key drug in short-course antitubercular chemotherapy.
  • Hyperuricemia and associated arthralgias are common side effects of PZA, caused by its metabolite pyrazinoic acid inhibiting renal urate secretion.
  • Allopurinol (Al), a hypouricemic agent, has shown limited clinical benefit in managing this side effect.

Purpose of the Study:

  • To investigate the pharmacokinetic interactions between PZA and Allopurinol.
  • To determine the effect of Allopurinol on PZA metabolites, particularly pyrazinoic acid levels and their impact on uric acid secretion.

Main Methods:

  • A cross-over study involving six healthy volunteers.
  • Administration of a single oral dose of PZA alone, and in a separate trial, PZA with Allopurinol.

Related Experiment Videos

  • Quantification of plasma and urinary concentrations of PZA and its metabolites using high-performance liquid chromatography (HPLC).

    • Main Results:

    • Allopurinol significantly altered the levels of PZA metabolites, leading to an accumulation of pyrazinoic acid.
    • Despite reducing uric acid synthesis, Allopurinol increased plasma concentrations of pyrazinoic acid.
    • This increase in pyrazinoic acid exacerbated the inhibition of renal urate secretion.

    Conclusions:

    • Allopurinol is ineffective and potentially detrimental in managing PZA-induced hyperuricemia due to increased pyrazinoic acid levels.
    • Alternative therapeutic strategies that do not involve xanthine oxidase inhibition are recommended for treating this chemotherapy side effect.