Rabbit Anti-Human NPC1L1 Polyclonal Antibody

Ezetimibe (EZT) is a selective cholesterol absorption inhibitor with poor aqueous solubility (0.012mg/ml 23 degrees C) and low oral bioavailability (about 35-65% for a once 10mg dose). The present study illustrates the preparation and characterization of two new co-crystals of ezetimibe using maleic acid and isonicotinamide as the coformers by solid grinding method. The co-crystal structures were characterized by X-ray powder diffraction (PXRD), differential scanning calorimetry (DSC), infrared spectroscopy (IR) techniques. Crystallinity and surface morphological characteristics of these prepared co-crystals were observed by scanning electron microscope (SEM). Dissolution rate tests demonstrated that both of the new co-crystals showed significant improvement in sodium lauryl sulfate -sodium acetate buffer solution (PH=4.5) at 15min and 20min. This study enriched the types of EZT co-crystals and identified that pharmaceutical co-crystal engineering technique play an important role in the dissolution rate enhancement of ezetimibe.

Quetiapine, one of the most prescribed atypical antipsychotics, has been associated with hyperlipidemia and an increased risk for cardiovascular disease in patients, but the underlying mechanisms remain unknown. Here, we identified quetiapine as a potent and selective agonist for pregnane X receptor (PXR), a key nuclear receptor that regulates xenobiotic metabolism in the liver and intestine. Recent studies have indicated that PXR also plays an important role in lipid homeostasis. We generated potentially novel tissue-specific PXR-KO mice and demonstrated that quetiapine induced hyperlipidemia by activating intestinal PXR signaling. Quetiapine-mediated PXR activation stimulated the intestinal expression of cholesterol transporter Niemann-Pick C1-Like 1 (NPC1L1) and microsomal triglyceride transfer protein (MTP), leading to increased intestinal lipid absorption. While NPC1L1 is a known PXR target gene, we identified a DR-1-type PXR-response element in the MTP promoter and established MTP as a potentially novel transcriptional target of PXR. Quetiapine's effects on PXR-mediated gene expression and cholesterol uptake were also confirmed in cultured murine enteroids and human intestinal cells. Our findings suggest a potential role of PXR in mediating adverse effects of quetiapine in humans and provide mechanistic insights for certain atypical antipsychotic-associated dyslipidemia.