Impact of amphotericin B on the cytochrome P450 system in HIV-infected patients

Eur J Med Res. 2004 Feb 27;9(2):51-4.

Abstract

Objective: To investigate whether cytochrome P450-dependent enzymes are influenced by amphotericin B (Am-B) during the treatment of Candida oesophagitis in HIV-infected patients.

Methods: Twelve HIV-infected, antiretroviral-naive patients (CDC/WHO stage C3) with Candida oesophagitits were enrolled into a prospective clinical trial. The patients were treated with Am-B (0.4 mg/kg body weight) for two weeks. At baseline and after Am-B therapy the clearance of antipyrine and its metabolites were investigated by high-performance liquid chromatography. In addition, the urinary excretion of 6-beta-hydroxycortisol and 17-hydroxycorticosteroids was assessed by means of a radioimmunoassay.

Results: The following significant changes were observed after Am-B treatment (P < 0.01): increase of antipyrine half-life (12.4 h vs 16.8 h) and the area under the plasma concentration-time curve (27.9 mg min/ml vs 38.1 mg min/ml); decrease of the total body clearance (61.2 ml/min vs 43.7 ml/min); decrease of the renal clearance of antipyrine metabolites - norantipyrine (7.45 ml/min vs 5.31 ml/min), 4-hydroxyantipyrine (15.4 ml/min vs 10.3 ml/min), hydroxymethylantipyrine (4.31 ml/min vs 3.65 ml/min); decrease of urinary 6-beta-hydroxycortisol excretion (453 microg/24h vs 298 microg/24h) and the ratio of 6-beta-hydroycortisol to 17-hydroxycorticosteroids (8.8% vs 6.4%).

Conclusions: Our data indicate that Am-B therapy has an inhibitory effect on cytochrome P450-dependent enzymes in HIV-infected patients. These results are of particular significance for HIV-infected patients who are concomitantly treated with drugs that are predominantly metabolised in the liver. A careful drug monitoring system seems advisable, especially for proteinase inhibitor experienced HIV-1-infected subjects.

Publication types

  • Clinical Trial

MeSH terms

  • 17-Hydroxycorticosteroids / urine
  • AIDS-Related Opportunistic Infections / drug therapy
  • AIDS-Related Opportunistic Infections / enzymology*
  • AIDS-Related Opportunistic Infections / urine
  • Amphotericin B / pharmacology*
  • Anti-Bacterial Agents / pharmacology
  • Antipyrine / pharmacokinetics
  • Candidiasis / complications
  • Chromatography, High Pressure Liquid
  • Cytochrome P-450 Enzyme System / drug effects*
  • Cytochrome P-450 Enzyme System / metabolism
  • Esophagitis / drug therapy
  • Esophagitis / etiology
  • Esophagitis / microbiology
  • Humans
  • Hydrocortisone / analogs & derivatives*
  • Hydrocortisone / urine
  • Immunocompromised Host

Substances

  • 17-Hydroxycorticosteroids
  • Anti-Bacterial Agents
  • 6 beta-hydroxycortisol
  • Amphotericin B
  • Cytochrome P-450 Enzyme System
  • Antipyrine
  • Hydrocortisone