OBJECTIVETo investigate the pharmacokinetics profile of fangchinoline and tetrandrine in rats after administration of single compound and mixture with other intergradient in traditional prescription.

METHODA method for determination of fangchinoline and tetrandrine in rat plasma by using HPLC-MS has been developed and validated. The pharmacokinetics of two compounds and two compounds in the effective component group (ECG) of Xiaoxuming decoction were compared.

RESULTCompared with the single dose of compound experiment results, the t(max) of fangchinoline and tetrandrine were longer than those in the single dose of ECG experiment. At the meanwhile the rest parameter showed no significant difference.

CONCLUSIONOther components in the ECG of Xiaoxuming decoction delayed the absorption rate of fangchinoline and tetrandrine, the bioavailability of two compounds were the same as that of the single dose of compound experiment.

Animals ; Benzylisoquinolines ; administration & dosage ; pharmacokinetics ; Drugs, Chinese Herbal ; administration & dosage ; pharmacokinetics ; Rats ; Rats, Wistar

Objective:To explore the risk factors of abdominal hemorrhage (AH) in patients with severe acute pancreatitis (SAP) and its impact on outcome.Methods:The clinical data of 231 SAP patients admitted to Diagnosis and Treatment Center for SAP of Guizhou Province from January 1, 2015 to December 31, 2019 were retrospectively analyzed. These patients were divided into AH group and non-AH group. The general information, etiology, acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score, sequential organ failure assessment (SOFA) score, organ failure, complications, interventions, bleeding time, bleeding site and outcome were compared between the two groups. Binary multivariate Logistic regression analysis was used to explore the risk factors of AH in SAP patients and whether the time and location of AH were risk factors affecting the outcome.Results:A total of 231 patients were enrolled in the analysis, including 198 patients without AH and 33 with AH (14.3%). There was no significant difference in gender, age or etiology between the two groups. The scores of APACHE Ⅱ and SOFA in AH group were significantly higher than those in non-AH group [APACHE Ⅱ score: 18 (12, 24) vs. 13 (9, 19), SOFA score: 9 (5, 15) vs. 5 (4, 11), both P < 0.01]. The incidences of acute kidney injury (AKI), gastrointestinal dysfunction, coagulation disorders, necrotic infection, pseudocyst and gastrointestinal fistula in AH group were significantly higher than those in non-AH group (66.7% vs. 47.0%, 36.4% vs. 7.1%, 18.2% vs. 6.6%, 66.7% vs. 9.1%, 66.7% vs. 34.3%, 9.1% vs. 1.5%, all P < 0.05). The proportions of requiring mechanical ventilation (MV) and surgical intervention in AH group were significantly higher than those in non-AH group (69.7% vs. 43.4, 48.5% vs. 14.6%, both P < 0.01). The length of intensive care unit (ICU) stay and hospital stay in AH group were significantly longer than those in non-AH group [length of ICU stay (days): 13 (8, 19) vs. 7 (3, 16), length of hospital stay: 24 (13, 40) vs. 17 (12, 24), both P < 0.01], and the hospital mortality was significantly higher (60.6% vs. 9.6%, P < 0.01). Multivariate Logistic regression analysis showed that APACHE Ⅱ score [odds ratio ( OR) = 1.157, 95% confidence interval (95% CI) was 1.030-1.299, P = 0.014], infectious necrosis ( OR = 12.211, 95% CI was 4.063-36.697, P < 0.01), pseudocyst ( OR = 3.568, 95% CI was 1.238-10.283, P = 0.019) and requiring MV ( OR = 0.089, 95% CI was 1.354-6.625, P = 0.007) were the risk factors of AH in SAP patients. In 33 AH patients, there was no significant difference in hospital mortality between early hemorrhage (occurred within 2 weeks of onset) and late hemorrhage (occurred 2 weeks after onset) groups [66.7% (8/12) vs. 57.1% (12/21), P > 0.05]. All 4 patients in the unspecified bleeding site group died during hospitalization; half or more patients died in the pseudocyst/abscess bleeding (14 cases), mesenteric/intestinal bleeding (13 cases) and gastric variceal bleeding (2 cases) groups (7 cases, 8 cases and 1 case respectively), and there were significant differences among the groups ( P < 0.05). Multivariate Logistic regression analysis showed that neither bleeding time ( OR = 0.989, 95% CI was 0.951-1.028, P = 0.574) nor bleeding site ( OR = 2.009, 95% CI was 0.822-4.907, P = 0.126) was the risk factor of death in patients with SAP combined with AH. Conclusions:Both early and late bleeding significantly increased the length of hospital stay and mortality of SAP patients. APACHE Ⅱ score, infectious necrosis and pseudocyst were the risk factors of AH in SAP patients. Neither bleeding time nor bleeding site was the risk factors of death in patients with SAP combined with AH. However, it still needed to be confirmed by a large sample clinical study.