Effect of food on everolimus absorption: quantification in healthy subjects and a confirmatory screening in patients with renal transplants

Pharmacotherapy. 2002 Feb;22(2):154-9. doi: 10.1592/phco.


Study objective: To quantify the influence of a high-fat meal on the oral bioavailability of the immunosuppressant everolimus in a single-dose study in healthy subjects and to confirm the results in a small food-effect screening assessment in patients with renal transplants who were receiving multiple-dose everolimus.

Design: Randomized, open-label, crossover, single-dose study and confirmatory screening.

Setting: Phase 1 unit for the single-dose study and two German hospitals for the patient screening.

Subjects: Twenty-four healthy male volunteers; six clinically stable patients with renal transplants who were originally part of a phase I dose-escalation study.

Intervention: The 24 healthy men received everolimus 2 mg orally under fasting conditions and after a high-fat meal. The six patients received everolimus 2.5 mg/day orally, in addition to cyclosporine and prednisone. On two occasions, a pharmacokinetic profile was obtained over the dosing interval after drug administration under fasting conditions and after a high-fat meal in a randomized sequence.

Measurements and main results: In the single-dose study in healthy subjects, a high-fat meal delayed everolimus time to maximum concentration (Tmax) by a median 1.25 hours, reduced peak blood concentration (Cmax) by 60%, and reduced area under the concentration-time curve (AUC) by 16%. In the multiple-dose screening in patients with renal transplants, a high-fat meal delayed Tmax by a median 1.75 hours and reduced Cmax by 53% and AUC by 21%. Everolimus trough levels showed no food effect, whereas the peak-trough fluctuation was dampened by 52%.

Conclusions: A high-fat meal modestly reduced everolimus AUC. To minimize longitudinal variability in exposure, everolimus should be administered consistently either with food or without food.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Area Under Curve
  • Biological Availability
  • Cross-Over Studies
  • Cyclosporine / pharmacokinetics
  • Dietary Fats / pharmacology*
  • Drug Interactions
  • Everolimus
  • Fasting / blood
  • Half-Life
  • Headache / chemically induced
  • Humans
  • Immunosuppressive Agents / adverse effects
  • Immunosuppressive Agents / blood
  • Immunosuppressive Agents / pharmacokinetics*
  • Kidney Transplantation
  • Middle Aged
  • Prednisone / pharmacokinetics
  • Sirolimus / adverse effects
  • Sirolimus / analogs & derivatives
  • Sirolimus / blood
  • Sirolimus / pharmacokinetics*
  • Time Factors


  • Dietary Fats
  • Immunosuppressive Agents
  • Cyclosporine
  • Everolimus
  • Prednisone
  • Sirolimus