Maintenance time of sedative effects after an intravenous infusion of diazepam: A guide for endoscopy using diazepam

AIM: To examine whether the sedative effects assessed by psychomotor tests would depend on the cytochrome P450 (CYP ) 2C19 genotypes after an infusion regimen of diazepam commonly used forgastrointestinal endoscopy in Japan. METHODS: Fifteen healthy Japanese volunteers consisting of three different CYP2C19 genotype groups underwent a critical ? icker fusion test, an eye movement analysis and a postural sway test as a test for physical sedative effects, and a visual analog scale (VAS) symptom assessment method as a test for mental sedative effects during the 336 h period after the intravenous infusion of diazepam (5 mg). RESULTS: The physical sedative effects assessed by the critical flicker test continued for 1 h (t values of 5 min, 30 min and 60 min later: 4.35, 5.00 and 3.19, respectively) and those by the moving radial area of a postural sway test continued for 3 h (t values of 5 h, 30 h, 60 min and 3 h later: -4.05, -3.42, -2.17 and -2.58, respectively), which changed significantly compared with the baseline level before infusion (P < 0.05). On the other hand, the mental sedative effects by the VAS method improved within 1 h. The CYP2C19 genotype-dependent differences in the postinfusion sedative effects were not observed in any of the four psychomotor function tests. CONCLUSION: With the psychomotor tests, the objective sedative effects of diazepam continued for 1 h to 3 h irrespective of CYP2C19 genotype status and the subjective sedative symptoms improved within 1 h. Up to 3 h of clinical care appears to be required after the infusion of diazepam, although patients feel subjectively improved.

Effect and safety of anaprazole in the treatment of duodenal ulcers:a randomized,rabeprazole-controlled,phase Ⅲ non-inferiority study

Background:The pharmacokinetic and clinical behaviors of many proton pump inhibitors(PPIs)in peptic ulcer treatment are altered by CYP2C19 genetic polymorphisms.This non-inferiority study evaluated the efficacy and safety of the novel PPI anaprazole compared with rabeprazole.We also explored the influence of Helicobacter pylori(H.pylori)infection status and CYP2C19 polymorphism on anaprazole.Methods:In this multicenter,randomized,double-blind,double-dummy,positive-drug parallel-controlled,phase Ⅲ study,Chinese patients with duodenal ulcers were randomized 1:1 to receive rabeprazole 10 mg+anaprazole placebo or rabeprazole placebo+anaprazole 20 mg once daily for 4 weeks.The primary efficacy endpoint was the 4-week ulcer healing rate assessed by blinded independent review.Secondary endpoints were the proportion of patients with improved overall and individual duodenal ulcer symptoms at 4 weeks.Furthermore,exploratory subgroup analysis of the primary endpoint by H.pylori status and CYP2C19 polymorphism was conducted.Adverse events were monitored for safety.Non-inferiority analysis was conducted for the primary endpoint.Results:The study enrolled 448 patients(anaprazole,n=225;rabeprazole,n=223).The 4-week healing rates were 90.9%and 93.7%for anaprazole and rabeprazole,respectively(difference,-2.8%[95%confidence interval,-7.7%,2.2%]),demonstrating non-inferiority of anaprazole to rabeprazole.Overall duodenal ulcer symptoms improved in 90.9%and 92.5%of patients,respectively.Improvement rates of individual symptoms were similar between the groups.Healing rates did not significantly differ by H.pylori status or CYP2C19 genotype for either treatment group.The incidence of treatment-emergent adverse events was similar for anaprazole(72/220,32.7%)and rabeprazole(84/219,38.4%).Conclusions:The efficacy of anaprazole is non-inferior to that of rabeprazole in Chinese patients with duodenal ulcers.Registration:ClinicalTrials.gov,NCT04215653.