Oral Bioavailability and Pharmacokinetics of Sildenafil Orally Disintegrating Tablets under Various Gastric pH Levels Following Administration of Omeprazole in Rats.

Sildenafil citrate, an oral drug used to treat erectile dysfunction, has low water solubility and oral bioavailability. The solubility is greatly influenced by the pH, changing from 37.25 mg/mL to 0.22 mg/mL with a change in pH from 1.2 to 8.0. This indicates that the absorption may decrease in patients who use drugs, such as proton pump inhibitors (PPIs), for gastroesophageal reflux disease. To improve the absorption of sildenafil citrate at various gastric pH levels, a sildenafil citrate orally disintegrating tablet (ODT), which has a rapid disintegration feature, was produced by a 3D printing technique. Our study investigated the pharmacokinetic parameters of the sildenafil citrate ODT in rats after oral administration and compared the absorption of the sildenafil citrate ODT and sildenafil citrate commercial tablet (RLD), with and without PPI treatment. The LC/MS/MS analysis of the plasma sildenafil concentration revealed that the area under curve from time 0 to infinity (AUC0-∞) of sildenafil in the sildenafil citrate ODT group was significantly higher than in the sildenafil citrate RLD group whether it was in combination with the PPI or not (274.8% and 144%, respectively; p < 0.05). The relative systemic bioavailability of sildenafil citrate RLD significantly decreased with the PPI, but that of sildenafil citrate ODT was not affected by the PPI. These results indicate that the relative systemic bioavailability of sildenafil citrate ODT was increased when it was prepared using the 3D printing technique and the absorption of this formulation was not affected by the PPI.

Efficacy evaluation of Chinese herbal medicine, VGH-BPH1, for patients with benign prostatic hyperplasia: A randomized, double-blind, placebo-controlled, and crossover study.

BACKGROUND: Benign prostatic hyperplasia (BPH) can affect quality of life and cause various complications. Previous studies have suggested that Chinese herbal medicine can alleviate symptoms in patients with BPH. This study aimed to investigate whether the Chinese herbal medicine prescription VGH-BPH1 can alleviate BPH symptoms when used as an add-on treatment. METHODS: In this crossover, randomized, double-blind, placebo-controlled trial, patients with BPH were randomly segregated into two groups: group A received VGH-BPH1, and group B received a placebo for 8 weeks. Subsequently, after a 2-week wash-out period, the two groups were switched to the opposite treatment for another 8 weeks. The International Prostate Symptoms Score and Aging Male Symptoms Score were adopted as the primary outcomes to assess improvement in BPH and patient quality of life. The secondary outcomes were the International Index of Erectile Function, Constitution Chinese Medicine Questionnaire, uroflowmetry results, and postvoid residual urine volume. RESULTS: VGH-BPH1 treatment significantly decreased the International Prostate Symptoms Score total score (p = 0.027); however, no significant difference was observed between the treatment and placebo groups. The Aging Male Symptoms Score "joint pain and muscular ache" score in the VGH-BPH1 group was significantly lower than that of the placebo group (p = 0.022). The "physical exhaustion" score also exhibited a decreasing trend when both groups were compared (p = 0.057). CONCLUSION: Although VGH-BPH1 treatment did not outperform the placebo in terms of improving BPH symptoms, it resulted in improvement in several quality of life indicators when relative to the placebo. Future research using a larger sample size with appropriate amendments to the protocol should be conducted to further investigate the effects of VGH-BPH1.

Synthesis and Bioassay of Neurogenically Potent Gangliosides DSG-A, Hp-s1 and Their Analogues.

In the search of a potent candidate for neurotherapy, we designed and synthesized various analogues of ganglioside Hp-s1. The modification includes the change in hydrophobicity by varying the carbon chain length, altering the number of hydrogen bonds, and replacing the anomeric atom. The chemical synthesis was carried out by using various methods and discussed in details. The neuritogenic activities of these analogues are confirmed in a human neuroblastoma cell line SH-SY5Y. A higher activity of ganglioside Hp-s1 analogue on IL-17A transcript upregulation than ganglioside Hp-s1 was found.

Clinical evaluation of insulin resistance and beta-cell function by the homeostasis model assessment in patients with systemic lupus erythematosus.

The aim of this preliminary study was to evaluate insulin resistance and secretion using homeostasis model assessment (HOMA) in patients with systemic lupus erythematosus (SLE). The fasting glucose and insulin concentrations, HOMA insulin resistance (IR), HOMA beta-cell, antidouble-stranded DNA antibodies (anti-dsDNA), C3, C4, and SLE disease activity index (SLEDAI) were determined in a total of 58 female SLE patients. All patients were classified into subgroups according to the presence of anticardiolipin antibodies (aCL+ vs. aCL-) and SLEDAI scores (SLEDAI < 3 vs. SLEDAI > 3). Results showed that SLE patients with and without aCL had significantly higher fasting insulin levels, HOMA IR, and HOMA beta-cells than controls. Similar results were also found in SLE patients with different disease activities. Pearson's correlation analysis showed that there was a highly significant correlation of HOMA IR with fasting insulin concentration in the SLE patients and SLE subgroups overall. However, HOMA beta-cells were positively correlated with HOMA IR and fasting insulin level, but negatively correlated with fasting glucose concentration in SLE patients overall. In conclusion, SLE patients, regardless of the presence of aCL and different disease activities, had a higher risk of insulin resistance and abnormal insulin secretion than age-matched healthy controls, based on fasting insulin concentration, HOMA IR, and HOMA beta-cells.