Pharmacokinetic evaluation and relative bioavailability pilot study of fidaxomicin in healthy Chinese subjects: An open, randomized, single-dose, cross-over study.

OBJECTIVE: To compare the pharmacokinetic (PK) characteristics, investigate relative bioavailability, and provide data for potential additional bioequivalence trials between generic fidaxomicin (test (T) formulation) and the original brand (reference (R) formulation) in healthy Chinese subjects. MATERIALS AND METHODS: An open, randomized, single-dose, cross-over study was conducted in 18 healthy Chinese subjects. The subjects randomly received T or R formulations and the alternative formulations were received after a 14-day wash-out period. Blood and fecal samples were collected and tested by liquid chromatography-tandem mass spectrometry (LC-MS/MS). PK parameters were calculated using a non-compartmental model. Relative bioavailability considering commonly established bioequivalence criteria was assessed. RESULTS: Cmax were 3.58 ± 2.74 ng/mL and 6.01 ± 3.93 ng/mL, and AUC0-∞ were 35.71 ± 18.68 h×ng/mL and 52.15 ± 31.31 h×ng/mL for the T and R formulations, respectively. The tmax of both formulations was 5.00 hours. The cumulative fecal excretion rate (Fe0-96h/F) of fidaxomicin and its main active metabolite OP-1118 were similar for both formulations. The geometric mean ratios and 90% confidence intervals (CI) of AUC0-t, AUC0-∞, and Cmax were not completely within the range of 80.00 - 125.00%. Significant within-subject and inter-subject coefficients of variation (> 30%) were found. CONCLUSION: Despite the differences in exposure, PK characteristics and fecal recovery of the two formulations were similar, suggesting that an effective concentration of the generic fidaxomicin could be achieved locally in the gastrointestinal tract. Fidaxomicin was a highly viable drug, thus providing reference for future clinical study design.

Pharmacokinetics and Safety of Single-Dose Amphotericin B Colloidal Dispersion in Healthy Chinese Subjects and Population Pharmacokinetic/Pharmacodynamic Analysis to Inform Clinical Efficacy in Invasive Infections Caused by Candida albicans.

PURPOSE: Amphotericin B colloidal dispersion (ABCD) is a less toxic formulation of amphotericin B for the treatment of invasive fungal infections. The pharmacokinetic (PK) profile and safety of a generic ABCD were investigated after a single dose (0.5 to 1.5 mg/kg) administered as an intravenous infusion in 30 healthy Chinese subjects. METHODS: PK data from healthy Chinese male subjects were applied for developing a population PK model to predict the PK profiles of standard doses (3 or 4 mg/kg) in patients. A 5000-time Monte Carlo simulation of AUC0-24/MIC target was implemented to determine the probability of target attainment (PTA) and cumulative fraction of response (CFR) under standard doses. FINDINGS: The PK profiles of intravenous administration of ABCD were best described by a 3-compartmental model with a time-varying clearance and a dose-dependent volume of distribution in the peripheral compartment. PK/pharmacodynamic (PK/PD) analysis revealed that 3 or 4 mg/kg ABCD once a day resulted in favorable CRF (>98%) with 2-log reduction of Candida albicans. A high PTA (>90%) was achieved at MIC ≤2 mg/L for the dosing regimen of ABCD 3 mg/kg and 4 mg/kg for MIC ≤4 mg/L. IMPLICATIONS: PK/PD analysis indicated that a favorable efficacy of ABCD could be reached at a dose of 3 or 4 mg/kg once daily for 14 to 28 days to treat invasive fungal infections caused by C albicans. ClinicalTrials.gov identifier: NCT03577509.

A prospective study on the treatment of immediate post-operative scar with narrowband intense pulsed light under polarized dermoscopy.

(a) To evaluate the efficacy and safety of narrow-band intense-pulsed light (DPL) in immediate post-operative scar. (b) To observe the process of scar formation under dermoscopy in the first 6 months. Nine patients with postoperative scars were enrolled in the randomized, prospective, split-scar study. Patients were treated in one half of the scar with DPL for cosmetic improvement at a wavelength of 500-600 nm and the other half was not treated as control. The laser treatments were initiated 2 weeks after the surgery and were given 3 times over a 4-week period. All patients were followed-up for 3 months from the last treatment. Photographs and dermoscopy digital images were collected each time. (a) Neither DPL or control produce statistically significant improvements in Vancouver Scar Scale. Moreover, comparatively, there was no statistical difference in Vancouver Scar Scale between DPL or control. However, 6 out of 9 patients treated with DPL had reduced scores in vascularity sooner compared with control. (b) Under dermoscopy, redness, and swelling were obvious from 2 weeks after surgery, but were gradually alleviated. The surface of the scar gradually became uneven and rough. DPL might be beneficial in early recovery of immediate post-operative scar.

Evaluation of Intravoxel Incoherent Motion Diffusion-Weighted Magnetic Resonance Imaging for Detection of Bowel Inflammation in Patients With Crohn Disease.

OBJECTIVES: This study aimed to evaluate the feasibility of intravoxel incoherent motion diffusion-weighted magnetic resonance imaging (DW-MRI) in detecting bowel inflammation in patients with Crohn disease (CD). METHODS: Sixteen patients who underwent intravoxel incoherent motion DW-MRI for CD and colonoscopy were recruited. Seventy-nine bowel segments were selected, and their mean D, D*, f, and apparent diffusion coefficient (ADC) values were measured. The receiver operating characteristic curve was performed to distinguish inflamed from normal bowel. RESULTS: The mean D, D*, f, and ADC values of inflamed bowel were significantly lower than those of normal bowel (P < 0.05). The area under the receiver operating characteristic curve for f (0.906) and ADC values (0.924) was greater than that for D (0.709) or D* values (0.686) for differentiating inflamed bowel from normal bowel (P < 0.05). CONCLUSIONS: Intravoxel incoherent motion DW-MRI is a feasible technique for detecting inflammation in CD patients. The ADC and f values have more potential than the D and D* values.

Prediction of loss to follow-up in long-term supportive periodontal therapy in patients with chronic periodontitis.

AIM: This study examined the predictors of loss to follow-up in long-term supportive periodontal therapy in patients with chronic periodontitis. METHODS: A total of 280 patients with moderate to severe chronic periodontitis in a tertiary care hospital in China were investigated and followed over the course of study. Questionnaires on clinical and demographic characteristics, self-efficacy for oral self-care and dental fear at baseline were completed. Participants were followed to determine whether they could adhere to long-term supportive periodontal therapy. Binary logistic regression analysis was used to examine the association between clinical and demographic characteristics, self-efficacy for oral self-care, dental fear and loss to follow-up in long-term supportive periodontal therapy. RESULTS: The loss to follow-up in long-term supportive periodontal therapy was significantly associated with age [adjusted OR = 1.042, 95% confidence interval (CI): 1.012-1.074, p = 0.006], severe periodontitis [adjusted OR = 4.892, 95%CI: 2.280-10.499, p<0.001], periodontal surgery [adjusted OR = 11.334, 95% CI: 2.235-57.472, p = 0.003], and middle and low-scoring of self-efficacy scale for self-care groups. The adjusted ORs of loss to follow-up for the middle- (54-59) and low-scoring groups (15-53) were 71.899 (95%CI: 23.926-216.062, p<0.001) and 4.800 (95% CI: 2.263-10.182, p<0.001), respectively, compared with the high-scoring SESS group (60-75). CONCLUSION: Age, severity of periodontitis, periodontal surgery and the level of self-efficacy for self-care may be effective predictors of loss to follow-up in long-term supportive periodontal therapy in patients with chronic periodontitis.

Expression of Glut-1 and HK-II in Pancreatic Cancer and Their Impact on Prognosis and FDG Accumulation.

OBJECTIVE: The purpose of this article is to analyze the expression of Glut-1 and HK-II, the association between their expression and 18F-FDG accumulation in pancreatic cancer. METHODS: Fifty patients with histologically proven pancreatic cancer were included in this preliminary study, all of whom received 18F-FDG PET/CT performance before surgery. Immunohistochemical staining of tumor tissue and adjacent normal tissue was performed for Glut-1 and HK-II. By combining proportions and intensity of immunochemical staining, we obtained the modified immunohistological scores for Glut-1 and HK-II respectively. The relationship between expression of Glut-1, HK-II and series of parameters was analyzed, i.e. clinicopathological characteristics, prognosis of patients and SUVmax of PET-CT. RESULTS: Compared with normal tissue, the Glut-1 and HK-II expression in pancreatic cancer tissue was significantly increased (P<.001). There was no correlation between expression of Glut-1, HK-II and age, gender, tumor size, tumor location, tumor histological type, tumor differentiation, the nerve infiltration, vascular invasion, local infiltration, lymph node metastasis or tumor staging in pancreatic cancer (P>.05). During the follow-up period, the survival curves of low Glut-1 group and high Glut-1 group were statistically different (P=.049). Multivariate analysis (Cox regression) revealed that Glut-1 expression was not associated with mortality (P>.05). No statistical difference was found in the survival curves of negative HK-II group and positive HK-II group (P=.545). There was no correlation between 18F-FDG uptake and expression of Glut-1 and HK-II(P>.05). CONCLUSION: The Glut-1 and HK-II expression in pancreatic cancer tissue was significantly increased. There was no correlation between expression of Glut-1, HK-II and clinicopathological characteristics, prognosis and 18F-FDG uptake.

Effect of recombinant Lactobacillus casei expressing interleukin-10 in dextran sulfate sodium-induced colitis mice.

OBJECTIVE: To study the effect of recombinant Lactobacillus casei (L.casei) expressing interleukin (IL)-10 combined with 5-aminosalicylic acid (5-ASA) in dextran sulfate sodium (DSS)-induced colitis mice. METHODS: Recombinant L. casei CECT 5276, which can secrete IL-10, was constructed. The length of colon tissue, disease activity index (DAI) and histological score (HS) of the mice were determined to evaluate the modeling and the effectiveness of L. casei. Real-time polymerase chain reaction (PCR), Western blot and ELISA were used to determine the levels of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), peroxisome proliferator-activated receptor (PPAR)-γ, interferon (IFN)-γ, transforming growth factor (TGF)-ß and IL-10. RESULTS: Recombinant L. casei expressing IL-10 combined with 5-ASA was more effective than L. casei with 5-ASA. Among the three different concentrations of the recombinant L. casei, the highest concentration group (2 × 10(9) colony-forming units/mL) had the best effectiveness. CONCLUSIONS: Recombinant L. casei combined with 5-ASA is effective in the treatment of DSS-induced colitis. The possible mechanism might be the blocking of the excessive activation of NF-κB pathway, thus suppressing the release of inflammation-related factors.