Abstract：
UNASSIGNED: Antiretrovirals have the potential to cause drug interactions leading to inefficacy or toxicity via induction of efflux transporters through nuclear receptors, altering drug concentrations at their target sites.
UNASSIGNED: This study used molecular dynamic simulations and qRT-PCR to investigate bictegravir\'s interactions with nuclear receptors PXR and CAR, and its effects on efflux transporters (P-gp, BCRP, MRP1) in rat PBMCs. PBMC/plasma drug concentrations were measured using LC-MS/MS to assess the functional impact of transporter expression.
UNASSIGNED: Bictegravir significantly increased the expression of ABC transporters, with Car identified as a key mediator. This suggests that bictegravir\'s influence on nuclear receptors could affect drug transport and efficacy at the cellular level.
UNASSIGNED: Bictegravir activates nuclear receptors enhancing efflux transporter expression. Understanding these interactions is crucial for preventing drug-drug interactions and reducing toxicity in clinical use. Combining CAR antagonists with bictegravir may prevent drug resistance and toxicity. However, these findings are based on preclinical data and necessitate further clinical trials to confirm their applicability in clinical settings.
UNASSIGNED: This study used molecular dynamic simulations and qRT-PCR to investigate bictegravir\'s interactions with nuclear receptors PXR and CAR, and its effects on efflux transporters (P-gp, BCRP, MRP1) in rat PBMCs. PBMC/plasma drug concentrations were measured using LC-MS/MS to assess the functional impact of transporter expression.
UNASSIGNED: Bictegravir significantly increased the expression of ABC transporters, with Car identified as a key mediator. This suggests that bictegravir\'s influence on nuclear receptors could affect drug transport and efficacy at the cellular level.
UNASSIGNED: Bictegravir activates nuclear receptors enhancing efflux transporter expression. Understanding these interactions is crucial for preventing drug-drug interactions and reducing toxicity in clinical use. Combining CAR antagonists with bictegravir may prevent drug resistance and toxicity. However, these findings are based on preclinical data and necessitate further clinical trials to confirm their applicability in clinical settings.
摘要：
■抗逆转录病毒药物有可能引起药物相互作用，通过激活外排转运蛋白通过核受体，导致无效或毒性，改变其靶位点的药物浓度。
■本研究使用分子动力学模拟和qRT-PCR来研究bictegravir与核受体Pxr和Car的相互作用，及其对外排转运蛋白的影响(P-gp，Bcrp,大鼠PBMC中的Mrp1)。使用LC-MS/MS测量PBMC/血浆药物浓度以评估转运蛋白表达的功能影响。
■Bictegravir显著增加ABC转运体的表达，汽车被确定为关键调解人。这表明bictegravir对核受体的影响可能会影响细胞水平的药物运输和功效。
■Bictegravir激活核受体，增强外排转运的表达。了解这些相互作用对于预防药物-药物相互作用和减少临床使用中的毒性至关重要。将Car拮抗剂与bictegravir联合使用可以防止耐药性和毒性。然而,这些发现是基于临床前数据，需要进一步的临床试验来确认其在临床环境中的适用性。
■本研究使用分子动力学模拟和qRT-PCR来研究bictegravir与核受体Pxr和Car的相互作用，及其对外排转运蛋白的影响(P-gp，Bcrp,大鼠PBMC中的Mrp1)。使用LC-MS/MS测量PBMC/血浆药物浓度以评估转运蛋白表达的功能影响。
■Bictegravir显著增加ABC转运体的表达，汽车被确定为关键调解人。这表明bictegravir对核受体的影响可能会影响细胞水平的药物运输和功效。
■Bictegravir激活核受体，增强外排转运的表达。了解这些相互作用对于预防药物-药物相互作用和减少临床使用中的毒性至关重要。将Car拮抗剂与bictegravir联合使用可以防止耐药性和毒性。然而,这些发现是基于临床前数据，需要进一步的临床试验来确认其在临床环境中的适用性。
