ABSTRACT
OBJECTIVE To study the pharmacokinetics of Esketamine hydrochloride nasal spray in rats and ciliary toxicity to maxillary mucosa of bullfrog. METHODS The plasma concentration of esketamine hydrochloride in rats was determined by LC-MS/ MS after intravenous injection of esketamine hydrochloride solution and nasal administration of esketamine hydrochloride； the pharmacokinetic parameters were calculated by using Phoenix WinNonlin 8.1.0 software. Using the maxillary mucosa of isolated bullfrog as a model， the morphological changes of maxillary mucosa were investigated， and the duration and recovery of ciliary oscillation were recorded after nasal administration of esketamine hydrochloride. RESULTS The peak of blood concentration occurred 2 min after nasal administration of esketamine hydrochloride； cmax was （814.58±418.80） ng/mL， AUC0－∞ was （203.75± 92.76） ng·h/mL， and the absolute bioavailability was 60.68%. After nasal administration of esketamine hydrochloride， it was observed that the cilia of bullfrog were arranged neatly， the edges were clear， the cilia tissue structure was complete and the cilia moved actively. The cilia movement time was （178.17±13.30） min for the first time， and after the cilia moved again， the ciliary movement time measured again was （24.50±9.19）min with a relative movement percentage of 53.56%. CONCLUSIONS Esketamine hydrochloride nasal spray has a rapid onset of action， high bioavailability， and low ciliary toxicity.
ABSTRACT
Objective To summarize the clinical experience of three different treatments for gallbladder and common bile duct stones.Methods The clinical data of 180 cases of gallbladder stones combined with bile duct stones undergoing surgery from May 2010 to May 2013 were retrospectively analyzed.They were divided into three groups,A group of 60 patients underwent a period of endoscopic sphincterotomy (EST),under the second phase of laparoscopic cholecystectomy (LC);Group B 60 patients underwent laparoscopic cholecystectomy (LC) + laparoscopic common bile duct exploration surgery (LCBDE) + T tube drainage;Group C 60 patients underwent conventional open cholecystectomy (OC) + bile duct exploration (OCBDE) + T tube drainage.Results A group of 53 cases completed surgery successfully,5 cases of remaining 7 patients failured in the first phase surgery,2 cases of the 5 patients did LC + LCBDE,3 of the 5 patients underwent conventional surgery.Two patients underwent the conventional surgery in the second phase surgery.B group of 57 cases completed surgery successfully,three cases convert to open surgery.All of the group C completed the surgery successfully.Group A complication was the most in the three groups (P＜0.05);group B had the shortest time of hospitalization (P＜0.05),the complication rate was lower than that in group A (P＜0.05),the complication had no significant difference between A and B.(P and group B ＞ 0.05),group B had shortest operation time (P＜0.05);no statistically significant differences were found among three groups in fasting time.Conclusion Three treatment methods have advantages as well as disadvantages,a reasonable treatment should be selected according to the specific circumstances.