Pharmacokinetics of two formulations of omeprazole administered through a gastrostomy tube in patients with severe neurodevelopmental problems

AIMS Omeprazole is often administered through a gastrostomy tube as either (i) a Multiple Unit Pellet System (MUPS (R)) tablet disintegrated in water (MUPS (R) formulation), or (ii) a suspension in 8.4% sodium bicarbonate (suspension formulation). This bioavailability study evaluates this practice in tube-fed patients with severe neurodevelopmental problems. METHODS Nonblinded, two-phase cross-over trial. RESULTS In seven of 10 patients, bioavailability was higher for the suspension formulation than for the MUPS (R) formulation. Median (90% confidence interval) area under the plasma concentration-time curve ratio (MUPS (R) over suspension) was 0.5 (0.06-2.37). CONCLUSIONS In this population, omeprazole MUPS (R) formulation has no apparent advantage over the more easily administered suspension formulation

The c-kit tyrosine kinase inhibitor STI571 for colorectal cancer therapy

The c-kit tyrosine kinase inhibitor STI571 exhibits a substantial therapeutic activity in patients with chronic myeloid leukemia and gastrointestinal stromal tumors respectively associated with constitutive activation of the BCR-ABL and c-kit tyrosine kinases. Human colorectal tumors also express the c-kit proto-oncogene. The present study focuses on the anticancer activity of STI571 in human colorectal tumor cells in vitro and in vivo. The c-kit receptor was identified as a M-r 145,000 immunoreactive band in human colon cancer cells HT29, HCT8/S11, and HCT116. Cellular invasion induced by 10 ng/ml stem cell factor (EC50 = 3 ng/ml) in HT29 cells was blocked by 1 mum STI571 (IC50 = 56 nM) and pharmacological inhibitors of several oncogenic signaling pathways, namely, phosphatidylinositol 3-kinase (LY294002), Rho GTPases (Clostridium botulinum exoenzyme C3 transferase), and Rho-kinase (Y27632). STI571 inhibited HT29 cell proliferation (IC50 = 6 muM) and induced apoptosis in vitro. These cellular effects were associated with a decrease in tumor growth. We also demonstrated that stem cell factor is a proangiogenic factor in vivo and in vitro. These encouraging results warrant further preclinical investigations and clinical trials on the use of the e-kit inhibitor STI571 as a chemotherapeutic agent in colon cancer prevention and in treatment of advanced colorectal cancers associated with liver metastases