GeneChip analysis determined that 37, 47, and 44 percent of the 12,559 gene sequences were expressed in 4-day andl6-day Caco-2 cells and human duodenum, respectively. Comparing human duodenum with Caco-2 cells, more than 1,000 sequences were determined to have at least a 5-fold difference in expression. There were 26, 38, and 44 percent of the 443 transporters, channels, and metabolizing enzymes detected in 4-day, 16-day Caco-2 cells, and human duodenum, respectively. More than 70 transporters and metabolizing enzymes exhibited at least a 3-fold difference. The overall coefficient of variability of the 10 human duodenal samples for all expressed sequences was 31% (range 3% to 294%) while that of the expressed transporters and metabolizing enzymes was 33% (range 3% to 87%). The in vivo / in vitro drug permeability measurements correlated well for passively absorbed drugs (R2 = 85%). The permeability correlation for carrier-mediated drugs showed 3- 35-fold higher in human above the correlation of passively absorbed drugs. The 2- 595-fold differences in gene expression levels between the Caco-2 cells and human duodenum correlated with the observed 3- 35-fold difference in permeability correlation between carrier-mediated drugs and passively absorbed drugs. CONCLUSIONS; Significant differences in gene expression levels in Caco-2 cells and human duodenum were observed. The observed differences of gene expression levels were consistent with observed differences in carrier mediated drug permeabilities. Gene expression profiling is a valuable new tool for investigating in vitro and in vivo permeability correlation.

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The majority of intensivists surveyed recognize stress-related mucosal bleeding as a relatively infrequent event; however, implementation of a stress ulcer prophylaxis risk stratification scheme for ICU patients is necessary. Histamine-2 receptor antagonists are consistently perceived as appropriate initial agents, although proton pump inhibitors have become first-line therapy in an increasing percentage of critical care patients, despite limited data regarding their use in this population.