To evaluate pharmacokinetic and metabolic characteristics of clevidipine butyrate lipid microspheres(CDB-LM)injection in mice, a novel HPLC-FLD method was developed for simultaneous measurement of clevidipine butyrate(CDB)and its metabolites clevidipine acid(MI)in whole blood samples. The chromatographic column was Waters C18(4. 6 mm×150 mm, 5 μm)and the mobile phase is consisted of acetonitrile-methanol-phosphate(2 ∶1 ∶2). The detection wavelength of FLD included excitation wavelength at 358 nm and emission wavelength at 440 nm. The pharmacokinetic parameters of CDB and MI were calculated by using DAS 2. 0. Then obtained parameters were statisticaly analyzed using PASW Statistics 18. The results showed that the half-life of CDB and MI were about 4 min and 20 min, respectively. Pharmacokinetic parameters of the low- and high-dose groups were as follows: CL of CDB were 4. 21 and 2. 72 L ·min-1 ·kg-1; AUC0-t were 3. 86 and 6. 43 mg/L ·min; MRT0-t were 7. 09 and 6. 17 min. CL of MI were 0. 34 and 0. 22 L ·min-1 ·kg-1; AUC0-t were 52. 23 and 74. 90 mg/L ·min; MRT0-t were 201. 24 and 217. 33 min. A method of protein precipitation was established, and acetonitrile was used to deal with whole blood samples. This method was simple, fast, with no interference with endogenous impurities. The results showed that the established HPLC-FLD method was simple and sensitive. It can be used to determine CDB and MI simultaneously. Comparing the low-dose group with the high-dose group, it was found that the plasma concentration-time curve of the two groups revealed the same tendency, which confirms that CDB has a short half-life and that it metabolizes to MI quickly.

Objective To analyze the difference and influential factors of clinical prognosis between liver transplantation with autoimmune liver disease (AILD) and viral hepatitis cirrhosis. Methods Clinical data of 75 recipients undergoing liver transplantation from January 2002 to January 2017 were retrospectively analyzed. All recipients were divided into the AILD group (n=25) and viral hepatitis cirrhosis group (n=50). The intraoperative conditions of the recipients were observed including warm ischemia time, cold ischemia time, operation time, anhepatic phase and blood transfusion volume. Postoperative complications were observed including severe acute kidney injury (AKI), infection, acute rejection, biliary tract-related complications, vascular-related complications and post transplantation diabetes mellitus (PTDM). The follow-up status were monitored after discharge. The prognostic factors of liver transplant recipients were analyzed. Results The warm ischemia time, cold ischemia time, operation time and anhepatic phase did not significantly differ between two groups (all P > 0.05). In the AILD group, the incidence of postoperative acute rejection was remarkably higher, whereas the incidence of postoperative severe AKI was significantly lower than those in the viral hepatitis cirrhosis group (both P < 0.05). The postoperative 1-, 3- and 5-year survival rates in the AILD group was 92%, 87%, and 87%, which did not significantly differ from 88%, 88% and 88% in the viral hepatitis cirrhosis group (all P > 0.05). Univariate analysis showed that age, model for end-stage liver disease (MELD) score, severe AKI, infection and biliary tract-related complications were the influencing factors of clinical prognosis of the recipients (all P < 0.05). Conclusions The overall survival prognosis does not significantly differ between the AILD and viral hepatitis cirrhosis groups. Age, MELD score, severe AKI, infection and biliary tract-related complications are the risk factors affecting the clinical prognosis of liver transplantation recipients.

Background: Hydrogen bonding interaction was considered to play a critical role in controlling drug release from transdermal patch. However, the quantitative evaluation of hydrogen bonding strength between drug and polar functional group was rarely reported, and the relationship between hydrogen bonding strength and controlled release capacity of pressure sensitive adhesive (PSA) was not well understood. The present study shed light on this relationship. Methods: Acrylate PSAs with amide group were synthesized by a free radical-initiated solution polymerization. Six drugs, , etodolac, ketoprofen, gemfibrozil, zolmitriptan, propranolol and lidocaine, were selected as model drugs. drug release and skin permeation experiments and pharmacokinetic experiment were performed. Partial correlation analysis, fourier-transform infrared spectroscopy and molecular simulation were conducted to provide molecular details of drug-PSA interactions. Mechanical test, rheology study, and modulated differential scanning calorimetry study were performed to scrutinize the free volume and molecular mobility of PSAs. Results: Release rate of all six drugs from amide PSAs decreased with the increase of amide group concentrations; however, only zolmitriptan and propranolol showed decreased skin permeation rate. It was found that drug release was controlled by amide group through hydrogen bonding, and controlled release extent was positively correlated with hydrogen bonding strength. Conclusion From these results, we concluded that drugs with strong hydrogen bond forming ability and high skin permeation were suitable to use amide PSAs to regulate their release rate from patch.