J Clin Pharmacol
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Sign In to gain access to subscriptions and/or personal tools.
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
0091270009333854v1
49/6/700    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Request Reprints
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Eley, T.
Right arrow Articles by Bertz, R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Eley, T.
Right arrow Articles by Bertz, R.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?

DRUG INTERACTIONS

Phase I Study of the Effect of Gastric Acid pH Modulators on the Bioavailability of Oral Dasatinib in Healthy Subjects

Timothy Eley, PhD, Feng R. Luo, PhD, Shruti Agrawal, MS, PhD, Ashish Sanil, PhD, James Manning, PhD, Tong Li, MD, Anne Blackwood-Chirchir, MD and Richard Bertz, PhD

From Discovery Medicine and Clinical Pharmacology (Dr Eley, Dr Luo, Dr Agrawal, Dr Sanil, Dr Li, Dr Bertz) and Pharmaceutical Candidate Optimization (Dr Manning) Bristol-Myers Squibb, Research and Development, Princeton, New Jersey; and Genentech, South San Francisco, California (Dr Blackwood-Chirchir).

Dasatinib is a tyrosine kinase inhibitor (including BCR-ABL and the SRC family) that is effective in patients with chronic myeloid leukemia. Dasatinib has pH-dependent solubility and is bioavailable as an oral formulation. The effect of gastric pH modifiers on dasatinib pharmacokinetics is evaluated in an open-label, randomized, 3-period, 3-treatment crossover study. Twenty-four healthy subjects receive treatment A (2 doses of dasatinib 50 mg separated by 12 hours), treatment B (famotidine 40 mg given 2 hours after dasatinib 50 mg and 10 hours before another dose of dasatinib 50 mg), and treatment C (30 mL of an antacid containing aluminum/magnesium hydroxides given 2 hours before dasatinib 50 mg and concomitantly with dasatinib 50 mg 12 hours after the previous dasatinib dose); a 7-day washout separates each treatment period. When famotidine is administered 2 hours after dasatinib, dasatinib exposure is similar to dasatinib administered alone. However, dasatinib exposure is reduced by ~60% when famotidine is administered 10 hours before dasatinib dosing. In contrast, dasatinib exposure is unchanged when antacid (Maalox) is administered 2 hours before dasatinib; but when the antacid is coadministered with dasatinib, dasatinib exposure is reduced by ~55% to 58%. This indicates that H2-receptor antagonists should not be coadministered with dasatinib. Dasatinib may be administered with acid-neutralizing antacids if the doses are temporally separated by at least 2 hours.

Key Words: Dasatinib • drug interaction • antacid • H2-receptor antagonist • pharmacokinetics

Address for reprints: Timothy Eley, PhD, Bristol-Myers Squibb Company, Mailstop: 8A-1.19, 311 Pennington-Rocky Hill Road, Hopewell, NJ 08534; e-mail: timothy.eley{at}bms.com.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?




HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2009 by the American College of Clinical Pharmacology