Establishing Virtual Bioequivalence and Clinically Relevant Specifications for Omeprazole Enteric-Coated Capsules by Incorporating Dissolution Data in PBPK Modeling.

Currently, Biopharmaceutics Classification System (BCS) classes I and III are the only biological exemptions of immediate-release solid oral dosage forms eligible for regulatory approval. However, through virtual bioequivalence (VBE) studies, BCS class II drugs may qualify for biological exemptions if reliable and validated modeling is used. Here, we sought to establish physiologically based pharmacokinetic (PBPK) models, in vitro-in vivo relationship (IVIVR), and VBE models for enteric-coated omeprazole capsules, to establish a clinically-relevant dissolution specification (CRDS) for screening BE and non-BE batches, and to ultimately develop evaluation criteria for generic omeprazole enteric-coated capsules. To establish omeprazole's IVIVR based on the PBPK model, we explored its in vitro dissolution conditions and then combined in vitro dissolution profile studies with in vivo clinical trials. The predicted omeprazole pharmacokinetics (PK) profiles and parameters closely matched the observed PK data. Based on the VBE results, the bioequivalence study of omeprazole enteric-coated capsules required at least 48 healthy Chinese subjects. Based on the CRDS, the capsules' in vitro dissolution should not be < 28%-54%, < 52%, or < 80% after two, three, and six hours, respectively. Failure to meet these dissolution criteria may result in non-bioequivalence. Here, PBPK modeling and IVIVR methods were used to bridge the in vitro dissolution of the drug with in vivo PK to establish the BE safety space of omeprazole enteric-coated capsules. The strategy used in this study can be applied in BE studies of other BCS II generics to obtain biological exemptions and accelerate drug development.

Rapid Detection and Quantification of Viable Cells of Pectobacterium brasiliense Using Propidium Monoazide Combined with Real-Time PCR.

Pectobacterium brasiliense (Pbr) has caused significant economic losses in major vegetable production areas in Northern China by causing bacterial soft rot in cash crops such as potatoes and cucumbers. This study aimed to establish a PMA-qPCR detection method for Pbr by screening specific and sensitive primers based on the glu gene and the conserved region of the 23S rRNA gene. Based on the optimized PMA pretreatment conditions, a standard curve was designed and constructed for PMA-qPCR detection (y = -3.391x + 36.28; R2 = 0.99). The amplification efficiency reached 97%, and the lowest detection limit of viable cells was approximately 2 × 102 CFU·mL-1. The feasibility of the PMA-qPCR method was confirmed through a manually simulated viable/dead cell assay under various concentrations. The analysis of potato tubers and cucumber seeds revealed that nine naturally collected seed samples contained a range from 102 to 104 CFU·g-1 viable Pbr bacteria. Furthermore, the system effectively identified changes in the number of pathogenic bacteria in cucumber and potato leaves affected by soft rot throughout the disease period. Overall, the detection and prevention of bacterial soft rot caused by Pbr is crucial.

Association between pulse wave velocity and hot flashes/sweats in middle-aged women.

As women age and go through menopause, they suffer a higher incidence of cardiovascular morbidity and mortality. Previous studies have shown that a relationship exists between hot flashes/sweats and an increased risk of cardiovascular disease. However, the association between hot flashes/sweats and arterial stiffness is unclear. We aim to explore the relationship between hot flashes/sweats and arterial stiffness using the modified Kupperman index (KMI) questionnaire and measure the brachial-ankle pulse wave velocity (baPWV). The prevalence of hot flashes in our research was reported to be 41.77%. There was a statistically significant difference between the mean baPWV among groups that experienced different severities of hot flashes/sweats according to one-way ANOVA test (p < 0.001). The baPWV values were positively associated with the severity of hot flashes/sweats based on linear regression after adjusting for established cardiovascular confounders (95% CI: (5.86, 43.23), p = 0.01). To the best of our knowledge, this study is the first investigation to propose that baPWV may serve both as an objective index for evaluating the severity of hot flashes/sweats and as a predictor of arterial stiffness beyond Cardiac Vascular Disease (CVD) risk factors in middle-aged women.

Sleep disorder, an independent risk associated with arterial stiffness in menopause.

As women age and go through menopause, they suffer a higher incidence of sleep disorder, cardiovascular morbidity and mortality. In addition, evidences suggested that sleep disorder was an important pathological indicator for coronary heart disease. However, the relationship between different menopausal status, sleep disorder and cardiovascular diseases was unclear. Thus, we aim to assess the association between sleep disorder with arterial stiffness in females of 40-60 years free of cardiovascular diseases through self-administered Pittsburgh Sleep Quality Index (PSQI) and brachial-ankle pulse wave velocity (baPWV). Logistic regression revealed that sleep disorder (PSQI score ≥ 8) was an independent indicator for higher risk of elevated arterial stiffness (baPWV ≥ 1465.5 cm/s, upper tertile) beyond other established cardiovascular confounders in peri-postmenopause (OR 2.83, 95% confidence interval (CI) 2.00-4.00, p < 0.001), but not in premenopause (OR 1.67, 95% CI 0.71-3.90, p = 0.223). Collectively, it clearly indicates that sleep disorder in menopausal women is of prominent value to predict arterial stiffness.