Effect of food on the pharmacokinetics of erlotinib, an orally active epidermal growth factor receptor tyrosine-kinase inhibitor, in healthy individuals.
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.
Ling
Jie
J
Genentech Inc., South San Francisco, California, USA.
Fettner
Scott
S
Lum
Bert L
BL
Riek
Myriam
M
Rakhit
Ashok
A
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000465:Algorithms; D019540:Area Under Curve; D003402:Creatine Kinase / Q000097:blood; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D000069347:Erlotinib Hydrochloride; D005076:Exanthema / Q000139:chemically induced; D005215:Fasting; D018565:Food-Drug Interactions; D005928:Glossitis / Q000139:chemically induced; D006417:Hematuria / Q000139:chemically induced; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D015394:Molecular Structure; D010352:Patient Dropouts / Q000706:statistics & numerical data; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D011799:Quinazolines / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics*; D013997:Time Factors; D005723:gamma-Glutamyltransferase / Q000097:blood
C487471:OSI-420; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; D005723:gamma-Glutamyltransferase; D066246:ErbB Receptors; D003402:Creatine Kinase