Effect of Drug Combination on Omeprazole Metabolism by Cytochrome P450 2C19 in Helicobacter pylori Eradication Therapy.

Helicobacter pylori (H. pylori) infection is common and can result in gastric and duodenal ulcers, and in some cases, gastric lymphoma and cancer. Omeprazole (OMP)-in combination with clarithromycin (CLR), amoxicillin (AMX), tinidazole (TND), or metronidazole (MET)-is used in double or triple combination therapy for eradication of H. pylori. However, the roles of the drugs other than OMP are not clearly understood. Therefore, in the present study, we aimed to investigate any effects of these drugs on OMP metabolism by wild-type CYP2C19 using spectroscopy and enzyme kinetics. The dissociation constants (Kd) for CYP2C19 with OMP, CLR, AMX, TND, and MET were 8.6, 126, 156, 174, and 249 µM, respectively. The intrinsic clearance of OMP was determined to be 355 mL/min/µmol of CYP2C19. Metabolism of OMP was significantly inhibited by 69, 66, 28, and 40% in the presence of CLR, TND, AMX, and MET, respectively. Moreover, the combination of CLR and TND resulted in 76% inhibition of OMP metabolism, while the combination of AMX and MET resulted in 48% inhibition of OMP metabolism. Both combinations of drugs not only have antibacterial effects, but also enhance the effect of OMP by inhibiting its metabolism by CYP2C19. These results indicate that drug-drug interactions of co-administered drugs can cause complex effects, providing a basis for OMP dose adjustment when used in combination therapy for H. pylori eradication.

A traditional Japanese medicine--Hangeshashinto (TJ-14)--alleviates chemoradiation-induced mucositis and improves rates of treatment completion.

PURPOSE: Oral mucositis induced by radiation or chemoradiation can cause devastating quality of life issues for patients undergoing treatment for head and neck cancer. In this study, we investigated the efficacy of a traditional Japanese medicine-Hangeshashinto (TJ-14)-for (chemo)radiation-induced oral mucositis. METHODS: Eighty patients who underwent whole neck radiation of >60 Gy with or without chemotherapy (high-dose cisplatin or low-dose docetaxel) were enrolled in this retrospective study; 40 had received TJ-14 during treatment, and 40 had not (controls). Factors related to alleviation of oral mucositis were identified by multivariate logistic regression analysis. Rates of completion of (chemo)radiation treatments were compared between the patients who received TJ-14 and the control group according to the treatment regimen. The comparison of the nutrition status between groups was also performed. RESULTS: Multivariate analysis indicated that the use of TJ-14 (p = 0.019), gender (p = 0.024), and primary tumor location (p = 0.028) were significant factors associated with the severity of oral mucositis. TJ-14 was associated with a significantly improved rate of completion of chemoradiation with cisplatin (p = 0.002). In the investigation of nutritional status, only serum albumin was significantly maintained better in the TJ-14 group than the control group in terms of mean change before and after (chemo)radiation (p = 0.024). CONCLUSIONS: The present study indicates that TJ-14 is effective for ameliorating oral mucositis induced by (chemo)radiation in patients with head and neck cancers. TJ-14 was associated with improved completion rates of chemoradiation treatments with cisplatin. A randomized controlled trial is necessary to confirm the efficacy of TJ-14 for chemoradiation-induced mucositis in head and neck cancer patients.

Boutonniere deformity of the second toe after planter dislocation of proximal interphalangeal joint: a case report.

The boutonniere deformity is a well-known deformity in the fingers, however, its appearance on a lessor toe is extremely rare. In the present case, the deformity resulted from a rupture of the central slip of the extensor tendon and the shift of the lateral bands to the planter side after reduction of a traumatic planter dislocation of the PIP joint of the second toe. Surgical repair of the extensor mechanism brought good results.