The erythromycin breath test as a predictor of cyclosporine blood levels

Clin Pharmacol Ther. 1990 Aug;48(2):120-9. doi: 10.1038/clpt.1990.126.

Abstract

The daily dose of cyclosporine required to attain a desired blood level can vary greatly among patients. Because elimination of cyclosporine depends on its metabolism in the liver by an enzyme (cytochrome P-450IIIA) that also demethylates erythromycin, we reasoned that the ability of patients to demethylate a test dose of erythromycin might be useful in estimating their appropriate daily doses of cyclosporine. Accordingly, the [14C-N-methyl] erythromycin breath test was administered to 32 patients before they received 3.0, 5.0, or 7.5 mg/kg/day cyclosporine to treat psoriasis. We found that a simple mathematical equation incorporating just the 14CO2 production, the age of the patient, and the daily dose of cyclosporine accounted for almost 80% (R2 = 0.78) of the interpatient variability in cyclosporine blood levels we observed. Our data indicate that P-450IIIA activity largely accounts for the relationship between dose of cyclosporine and blood levels for an individual patient. We conclude that the erythromycin breath test may be a convenient guide for cyclosporine dosing.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Breath Tests*
  • Carbon Dioxide / metabolism
  • Cyclosporins / blood*
  • Cyclosporins / metabolism
  • Cyclosporins / therapeutic use
  • Erythromycin*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Models, Theoretical
  • Predictive Value of Tests
  • Psoriasis / blood
  • Psoriasis / drug therapy
  • Regression Analysis

Substances

  • Cyclosporins
  • Carbon Dioxide
  • Erythromycin