PMID- 19740393
OWN - NLM
STAT- MEDLINE
DCOM- 20100416
LR  - 20240322
IS  - 1365-2125 (Electronic)
IS  - 0306-5251 (Print)
IS  - 0306-5251 (Linking)
VI  - 68
IP  - 3
DP  - 2009 Sep
TI  - Effect of a proton pump inhibitor on the pharmacokinetics of imatinib.
PG  - 370-4
LID - 10.1111/j.1365-2125.2009.03466.x [doi]
AB  - AIMS: Imatinib mesylate (Gleevec/Glivec), which has revolutionized the treatment 
      of chronic myeloid leukemias (CML) and gastrointestinal stromal tumours (GIST), 
      has been reported to cause gastric upset. Consequently, proton pump inhibitors 
      (PPI) are frequently co-administered with imatinib. Because PPI can elevate 
      gastric pH and delay gastric emptying or antagonize ATP-binding-cassette 
      transporters, they could influence imatinib absorption and pharmacokinetics. We 
      aimed to evaluate whether use of omeprazole has a significant effect on imatinib 
      pharmacokinetics. METHODS: Twelve healthy subjects were enrolled in a two-period, 
      open-label, single-institution, randomized cross-over, fixed-schedule study. In 
      one period, each subject received 400 mg imatinib orally. In the other period, 40 
      mg omeprazole (Prilosec) was administered orally for 5 days, and on day 5 it was 
      administered 15 min before 400 mg imatinib. Plasma concentrations of imatinib and 
      its active N-desmethyl metabolite CGP74588 were assayed by LC-MS, and data were 
      analyzed non-compartmentally. RESULTS: PPI administration did not significantly 
      affect the imatinib area under the plasma concentration vs time curve (AUC) (34.1 
      microg ml(-1) h alone vs 33.1 microg ml(-1) h with omeprazole, P= 0.64; 80% 
      power), maximum plasma concentration (C(max)) (2.04 microg ml(-1) alone vs 2.02 
      microg ml(-1) with omeprazole, P= 0.97), or half-life (13.4 h alone vs 14.1 h 
      with omeprazole, P= 0.13). CONCLUSIONS: Our results indicate that the use of 
      omeprazole does not significantly affect the pharmacokinetics of imatinib, as 
      opposed to, for example, dasatinib where PPI decreased AUC and C(max) two-fold.
FAU - Egorin, Merrill J
AU  - Egorin MJ
AD  - Molecular Therapeutics/Drug Discovery Program, University of Pittsburgh Cancer 
      Institute, Pittsburgh, PA 15213-1863, USA.
FAU - Shah, Dhvani D
AU  - Shah DD
FAU - Christner, Susan M
AU  - Christner SM
FAU - Yerk, Mara A
AU  - Yerk MA
FAU - Komazec, Kristin A
AU  - Komazec KA
FAU - Appleman, Leonard R
AU  - Appleman LR
FAU - Redner, Robert L
AU  - Redner RL
FAU - Miller, Brian M
AU  - Miller BM
FAU - Beumer, Jan H
AU  - Beumer JH
LA  - eng
GR  - UL1 RR024153/RR/NCRR NIH HHS/United States
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Br J Clin Pharmacol
JT  - British journal of clinical pharmacology
JID - 7503323
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Benzamides)
RN  - 0 (Piperazines)
RN  - 0 (Proton Pump Inhibitors)
RN  - 0 (Pyrimidines)
RN  - 8A1O1M485B (Imatinib Mesylate)
RN  - KG60484QX9 (Omeprazole)
SB  - IM
MH  - Administration, Oral
MH  - Adult
MH  - Antineoplastic Agents/metabolism/*pharmacokinetics
MH  - Benzamides
MH  - Chromatography
MH  - Female
MH  - Humans
MH  - Imatinib Mesylate
MH  - Male
MH  - Mass Spectrometry
MH  - Omeprazole/*pharmacology
MH  - Piperazines/metabolism/*pharmacokinetics
MH  - Proton Pump Inhibitors/*pharmacology
MH  - Pyrimidines/metabolism/*pharmacokinetics
PMC - PMC2766475
EDAT- 2009/09/11 06:00
MHDA- 2010/04/17 06:00
PMCR- 2010/09/01
CRDT- 2009/09/11 06:00
PHST- 2009/09/11 06:00 [entrez]
PHST- 2009/09/11 06:00 [pubmed]
PHST- 2010/04/17 06:00 [medline]
PHST- 2010/09/01 00:00 [pmc-release]
AID - BCP3466 [pii]
AID - 10.1111/j.1365-2125.2009.03466.x [doi]
PST - ppublish
SO  - Br J Clin Pharmacol. 2009 Sep;68(3):370-4. doi: 10.1111/j.1365-2125.2009.03466.x.