ABSTRACT
OBJECTIVE： To systematically evaluate effectiveness of prophylactic application of carbapenems for severe acute pancreatitis （SAP）， and to provide evidence-based reference in clinic. METHODS： Retrieved from PubMed， Embase， Medline， Cochrane Library， CNKI and VIP database，randomized controlled trials （RCTs） about effectiveness of prophylactic application of carbapenems （trial group） versus placebo or non-prophylactic use of antibiotics （control group） for SAP were included， and the retrieval time was from establishment to Dec. 2018. After extracting data from clinical studies that met the inclusion criteria， methodological quality of included studies were evaluated by using Cochrane bias risk assessment tool 5.1.0 and modified Jadad scoring scale， and Meta-analysis was performed for pancreatic infection rate， extrapancreatic infection rate， surgical intervention rate and mortality rate by using Rev Man 5.3 statistical software. RESULTS： A total of 8 RCTs were included， involving 544 patients. Meta-analysis showed that there was no statistical significance in the pancreatic infection rate [RR＝0.84， 95％CI （0.58， 1.22）， P＝0.36]， extra-pancreatic infection rate [RR＝0.76， 95％CI （0.43， 1.35）， P＝0.35] and surgical intervention rate [RR＝0.93， 95％CI （0.65， 1.32）， P＝0.68] or mortality rate [RR＝0.99， 95％CI（0.59，1.65）， P＝0.97] between 2 groups. CONCLUSIONS： The prophylactic use of carbapenems can not reduce pancreatic or extra-pancreatic infection rate， surgical intervention rate and mortality rate.
ABSTRACT
To investigate the pharmacokinetics of irinotecan hydrochloride (CPT-11) in rats and the tissue distribution of CPT-11 in mice after injection of irinotecan hydrochloride nanoparticles (CPT-11 NPs) via tail veins, separately, a LC-MS/MS method was established to determine the concentration of CPT-11 in whole blood of rats and in different tissues of mice. The pharmacokinetics and tissue distribution of CPT-11 were compared after the intravenous injection of CPT-11 NPs and CPT-11 solution. Compared with CPT-11 solution, the elimination half-life of CPT-11 was prolonged from 2.28 h to 3.95 h after the intravenous injection of CPT-11 NPs, and its AUC was 1.47 times than that of CPT-11 solution. After the injection of CPT-11 NPs in mice, the concentrations of CPT-11 loaded in CPT-11 NPs were significantly higher in the whole blood, colon and lungs than those in CPT-11 solution, but lower in the spleen, liver, kidney and heart, but the least in brain. CPT-11 NPs could improve CPT-11 's AUC, and help CPT-11 to reach long circulation activity.
ABSTRACT
The object of this study is to investigate the pharmacokinetic interaction of pioglitazone hydrochloride and atorvastatin calcium in healthy adult Beagle dogs following single and multiple oral dose administration. A randomized, cross-over study was conducted with nine healthy adult Beagle dogs assigned to three groups. Each group was arranged to take atorvastatin calcium (A), pioglitazone hydrochloride (B), atorvastatin calcium and pioglitazone hydrochloride (C) orally in the first period, to take B, C, A in the second period, and to take C, A, B in the third period for 6 days respectively. The blood samples were collected at the first and the sixth day after the administration, plasma drug concentrations were determined by LC-MS/MS, a one-week wash-out period was needed between each period. The pharmacokinetic parameters of drug combination group and the drug alone group were calculated by statistical moment method, calculation of C(max) and AUC(0-t) was done by using 90% confidence interval method of the bioequivalence and bioavailability degree module DAS 3.2.1 software statistics. Compared with the separate administration, the main pharmacokinetic parameters (C(max) and AUC(0-t)) of joint use of pioglitazone hydrochloride and atorvastatin calcium within 90% confidence intervals for bioequivalence statistics were unqualified, the mean t(max) with standard deviation used paired Wilcoxon test resulted P > 0.05. There was no significant difference within t1/2, CL(int), MRT, V/F. Pioglitazone hydrochloride and atorvastatin calcium had pharmacokinetic interaction in healthy adult Beagle dogs.