Effect of food on the pharmacokinetics of erlotinib, an orally active epidermal growth factor receptor tyrosine-kinase inhibitor, in healthy individuals

Anticancer Drugs. 2008 Feb;19(2):209-16. doi: 10.1097/CAD.0b013e3282f2d8e4.

Abstract

The effects of food on the pharmacokinetics of erlotinib were investigated in two open-label, randomized studies. In a single-dose crossover study (n = 18), 150 mg of erlotinib was administered under either fasting or fed conditions. In the first period, an approximate doubling in the area under the plasma concentration-time curve was evidenced by the geometric mean ratio (GMR) of 2.09 observed under fed conditions; whereas, in the second period there was a decrease, with a GMR of 0.93. In a multiple-dose parallel study (n = 22), 100 mg of erlotinib was administered daily for 8 days, either 7 days of fasting followed by feeding on day 8, or the reverse sequence. In this study, food resulted in an increase in the plasma concentration-time curve on day 1, with a GMR of 1.66 (P = 0.015). In contrast, there was only a 37% increase on day 7, with a GMR of 1.34 (P = 0.252). These studies indicate that food can substantially increase plasma exposure to erlotinib. Given the maximum tolerated dose of erlotinib used in clinical practice, we recommend that erlotinib be taken under conditions of fasting.

Publication types

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

MeSH terms

  • Administration, Oral
  • Adult
  • Aged
  • Algorithms
  • Area Under Curve
  • Creatine Kinase / blood
  • Cross-Over Studies
  • Dose-Response Relationship, Drug
  • ErbB Receptors / antagonists & inhibitors*
  • Erlotinib Hydrochloride
  • Exanthema / chemically induced
  • Fasting
  • Food-Drug Interactions*
  • Glossitis / chemically induced
  • Hematuria / chemically induced
  • Humans
  • Liver / drug effects
  • Liver / enzymology
  • Male
  • Middle Aged
  • Molecular Structure
  • Patient Dropouts / statistics & numerical data
  • Protein Kinase Inhibitors / administration & dosage
  • Protein Kinase Inhibitors / adverse effects
  • Protein Kinase Inhibitors / pharmacokinetics
  • Quinazolines / chemistry
  • Quinazolines / metabolism
  • Quinazolines / pharmacokinetics*
  • Time Factors
  • gamma-Glutamyltransferase / blood

Substances

  • OSI-420
  • Protein Kinase Inhibitors
  • Quinazolines
  • Erlotinib Hydrochloride
  • gamma-Glutamyltransferase
  • ErbB Receptors
  • Creatine Kinase