Early effects of lafutidine or rabeprazole on intragastric acidity: which drug is more suitable for on-demand use?

Background Medication for the relief of heartburn should have the rapid onset of action required for on-demand use. We studied the inhibition of gastric acid secretion by lafutidine and rabeprazole, given in single doses to fasting and postprandial subjects.Methods A total of 22 healthy male, Helicobacter pylori-negative volunteers participated in this randomized, two-way crossover study. They were randomly assigned to receive a single oral dose of 10mg lafutidine or 20mg rabeprazole after fasting overnight (12 subjects, fasting study) or after eating a test meal (noodles, 364kcal; protein, 10.1g; fat, 16g; carbohydrates, 44.9g; NaCl, 1.1g; 10 subjects, postprandial study). Intragastric pH was monitored continuously for 6h after treatment. The other drug was given after a washout period of at least 7 days, and intragastric pH was similarly monitored.Results In the fasting study, lafutidine sustained pH at >3 and >4 during the second, third, fourth, fifth, and sixth hours of the study for significantly longer than rabeprazole. During the first 6h after treatment, lafutidine sustained pH at more than 2, 3, 3.5, 4, 5, 6, and 7 longer than rabeprazole. In the postprandial study, lafutidine sustained pH >3 and >4 for longer periods than rabeprazole during the third, fourth, fifth, and sixth hours of the study. During the first 6h after treatment, lafutidine sustained pH at more than 2, 3, 3.5, 4, 5, 6, and 7 longer than rabeprazole.Conclusions Lafutidine 10mg produces a prompter rise in intragastric pH than rabeprazole 20mg in fasting and postprandial Helicobacter pylori-negative male subjects.     

Sofosbuvir plus ribavirin in Japanese patients with chronic genotype 2 HCV infection: an open‐label,phase 3 trial

Genotype 2 hepatitis C virus (HCV) accounts for up to 30% of chronic HCV infections in Japan. The standard of care for patients with genotype 2 HCV – peginterferon and ribavirin for 24 weeks – is poorly tolerated, especially among older patients and those with advanced liver disease. We conducted a phase 3, open‐label study to assess the efficacy and safety of an all‐oral combination of the NS5B polymerase inhibitor sofosbuvir and ribavirin in patients with chronic genotype 2 HCV infection in Japan. We enrolled 90 treatment‐naïve and 63 previously treated patients at 20 sites in Japan. All patients received sofosbuvir 400 mg plus ribavirin (weight‐based dosing) for 12 weeks. The primary endpoint was sustained virologic response at 12 weeks after therapy (SVR12). Of the 153 patients enrolled and treated, 60% had HCV genotype 2a, 11% had cirrhosis, and 22% were over the aged 65 or older. Overall, 148 patients (97%) achieved SVR12. Of the 90 treatment‐naïve patients, 88 (98%) achieved SVR12, and of the 63 previously treated patients, 60 (95%) achieved SVR12. The rate of SVR12 was 94% in patients with cirrhosis and in those aged 65 and older. No patients discontinued study treatment due to adverse events. The most common adverse events were nasopharyngitis, anaemia and headache. Twelve weeks of sofosbuvir and ribavirin resulted in high rates of SVR12 in treatment‐naïve and previously treated patients with chronic genotype 2 HCV infection. The treatment was safe and well tolerated by patients, including the elderly and those with cirrhosis.     

Inhibitory effects of lysophosphatidic acid receptor-5 on cellular functions of sarcoma cells

Abstract

Lysophosphatidic acid (LPA) is a bioactive lipid that interacts with G protein-coupled LPA receptors (LPA receptor-1 (LPA₁) to LPA₆). Here, we investigated the effects of LPA signaling via LPA₅ on cellular functions of sarcoma cells by generating Lpar5 overexpressing and Lpar5 knockdown cells from rat osteosarcoma and malignant fibrous histiocytoma cells, respectively. The cell motility activity of Lpar5 overexpressing cells was significantly lower, while Lpar5 knockdown cells showed high cell motility, compared with respective controls. Gelatin zymography showed that LPA₅ suppressed the activation of matrix metalloproteinase-2. LPA₅ also inhibited the cell motility activity of endothelial cells, correlating with the expression levels of vascular endothelial growth factor genes. These results suggest that LPA signaling via LPA₅ negatively regulates the cellular functions of rat sarcoma cells.