K. Shirakawa

CYP2C19 genotype–related efficacy of omeprazole for the treatment of infection caused by Helicobacter pylori

Omeprazole is used for the treatment of infection caused by Helicobacter pylori, and it is metabolized by the polymorphic cytochrome P4502C19 (CYP2C19). We have found that the anti–H pylori efficacy by the combination of omeprazole and antibiotics is related to the CYP2C19 genotype.

Interaction of docetaxel ('Taxotere') with human P-glycoprotein

The interaction of docetaxel (“Taxotere”) with P‐glycoprotein (P‐gp) was examined using porcine kidney epithelial LLC‐PK1 and LLC‐GA5‐COL150 cells, overexpressing human P‐gp selectively on the apical plasma membrane by transfection of human MDR1cDNA into the LLC‐PK1 cells. The basal‐to‐apical transport of [14C]docetaxel in LLC‐GA5‐COL150 cells significantly exceeded that in LLC‐PK1 cells, but the apical‐to‐basal transport was decreased in LLC‐GA5‐COL150 cells. The intracellular accumulation after its basal or apical application to LLC‐GA5‐COL150 cells was 4‐ to 20‐fold lower than that of LLC‐PK1 cells. Multidrug resistance (MDR) modulators, i.e., cyclosporin A and SDZ PSC 833, inhibited the basal‐to‐apical transport and increased the apical‐to‐basal transport of [14C] docetaxel in LLC‐GA5‐COL150 cells, but verapamil affected only apical‐to‐basal transport. The intracellular accumulation after basal or apical application to LLC‐GA5‐COL150 cells was also increased by these three MDR modulators. These observations demonstrated that docetaxel is a substrate for human P‐gp, suggesting that docetaxel‐drug interactions occur via P‐gp. The inhibition of [14C]docetaxel transport by the MDR modulators, as well as daunorubicin and vinblastine, was also found in LLC‐PK1 cells, which endogenously express P‐gp at lower levels, and concentrations showing similar levels of inhibition were lower than those in the case of LLC‐GA5‐COL150 cells. These observations indicate that it is necessary to consider the Pharmacokinetic and pharmacodynamic interactions of docetaxel via P‐gp.

Analysis of Helicobacter pylori vacA gene and serum antibodies to VacA in Japan.

Vacuolating cytotoxin, VacA, is one of the most important pathogenetic factors produced by Helicobacter pylori. However, it is not clear whether the diversity in disease outcome may be ascribed to variations in strain and/or to the host responses to virulence factors. In this study, we analyzed the vacA middle region sequence among 65 Japanese isolates to clarify the variation in strain and assayed antibody titer to VacA by ELISA using purified VacA to evaluate the host response to cytotoxin. The nucleotide sequence identities compared among Japanese isolates were 92.8 ± 3.56%, and compared to 88.3 ± 2.89% in tox+ strains reported in GenBank. Positive correlation was found between the antibody titers and the severity of atrophic change of the stomach. In Japan the nucleotide sequences of the vacA middle region were highly homologous and genetically closer to tox+ strains. Antibody titers and host response to cytotoxin may be associated with atrophy of the stomach.