Phase I pharmacokinetic studies evaluating single and multiple doses of oral GW572016, a dual EGFR-ErbB2 inhibitor, in healthy subjects

Aimee K. Bence, Eric B. Anderson, Maqbool A. Halepota, Michael A. Doukas, Phillip A. DeSimone, George A. Davis, Deborah A. Smith, Kevin M. Koch, Andrew G. Stead, Steve Mangum, Carolyn J. Bowen, Neil L. Spector, Showchien Hsieh, Val R. Adams

Research output: Contribution to journalArticlepeer-review

112 Scopus citations


GW572016 is a dual EGFR-ErbB2 inhibitor that has promise as an anticancer agent. Two phase I studies were conducted to determine the safety, tolerability and pharmacokinetics of single and multiple doses given to healthy subjects. The single dose study evaluated two groups of eight subjects in an ascending dose, 4-way cross-over, while the multiple dose study evaluated twenty-seven healthy volunteers in an ascending dose, double-blind, randomized, placebo-controlled, staggered parallel design. No serious adverse events were seen in either study. The most common adverse events for subjects receiving GW572016 were headache, diarrhea, rash, cold symptoms, gastrointestinal symptoms, and elevated LFTs, which were similar between treatment and placebo groups. Absorption of single doses of GW572016 was slightly delayed, with median t lag of 15 minutes (range 0-90 minutes) and achieved peak serum concentrations at a median of three hours (range 1.5-6 hours) post-dose. Serum concentrations after multiple doses of GW572016 demonstrated no significant accumulation at the 25 mg dose, and approximately 50% accumulation at the 100 mg and 175 mg doses, achieving steady state in six to seven days. A modest time-dependent increase in serum concentrations also was detected with multiple doses of GW572016. Single and multiple oral doses of GW572016 were well tolerated in healthy subjects, and resulted in dose-related systemic exposure of GW572016.

Original languageEnglish
Pages (from-to)39-49
Number of pages11
JournalInvestigational New Drugs
Issue number1
StatePublished - Jan 2005

Bibliographical note

Funding Information:
A. Bence was supported by a University of Kentucky Research and Graduate Studies fellowship. The authors wish to thank Jean Scott for editorial assistance with this manuscript. GlaxoSmithKline funded this study and provided GW572016. The authors are grateful to the study participants who volunteered for the study, as well as Susan Price and the other study nurses for their expert assistance with the study.


  • GW572016
  • phase I
  • signal transduction
  • tyrosine kinase inhibitor

ASJC Scopus subject areas

  • Oncology
  • Pharmacology
  • Pharmacology (medical)


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