Physiologically Based Pharmacokinetic Modeling to Unravel the Drug-gene Interactions of Venlafaxine: Based on Activity Score-dependent Metabolism by CYP2D6 and CYP2C19 Polymorphisms.

Background: Venlafaxine (VEN) is a commonly utilized medication for alleviating depression and anxiety disorders. The presence of genetic polymorphisms gives rise to considerable variations in plasma concentrations across different phenotypes. This divergence in phenotypic responses leads to notable differences in both the efficacy and tolerance of the drug.

Enhancing Paclitaxel Efficacy with Piperine-Paclitaxel Albumin Nanoparticles in Multidrug-Resistant Triple-Negative Breast Cancer by Inhibiting P-Glycoprotein.

Triple-negative breast cancer (TNBC) is a highly aggressive disease with rapid progression and poor prognosis due to multidrug resistance (MDR). Piperine (PIP) shows promise as a P-gp inhibitor, capable of sensitizing chemotherapeutic drugs and exhibiting antitumor properties. This study explores the inhibitory mechanism of PIP on P-glycoprotein (P-gp) and its capacity to enhance the sensitivity of paclitaxel (PTX).

Pharmacokinetics and absorption mechanism of tandospirone citrate.

Tandospirone citrate (TDS) is commonly used for the treatment of patients with generalized anxiety disorder in clinical practice, and several studies are developing new indications for TDS. However, the processes and absorption properties of TDS have not been systematically investigated. In this work, we conducted a comprehensive investigation using , , and approaches, involving animal and cellular models, to examine the pharmacokinetic properties and absorption mechanisms of TDS.

In vitro Assessment of the Effects of Silybin on CYP2B6-mediated Metabolism.

Silybin is a flavonol compound with a variety of physiological properties, such as hepatoprotective, anti-fibrogenic, and hypocholesterolemic effects. Although the and effects of silybin are frequently reported, studies on herb-drug interactions have yet to be performed. With the discovery of multiple important substrates of CYP2B6 recently, there is a growing body of evidence indicating that CYP2B6 plays a much larger role in human drug metabolism than previously thought.

High-fat diets enhance and delay ursodeoxycholic acid absorption but elevate circulating hydrophobic bile salts.

Ursodeoxycholic acid (UDCA) is a natural drug essential for the treatment of cholestatic liver diseases. The food effects on the absorption of UDCA and the disposition of circulating bile salts remain unclear despite its widespread global uses. This study aims to investigate the effects of high-fat (HF) diets on the pharmacokinetics of UDCA and disclose how the circulated bile salts were simultaneously perturbed.

Efficacy and safety of ursodeoxycholic acid in children with cholestasis: A systematic review and meta-analysis.

Objectives: Ursodeoxycholic acid (UDCA) is the main therapeutic drug for cholestasis, but its use in children is controversial. We conducted this study to evaluate the efficacy and safety of ursodeoxycholic acid in children with cholestasis.

Methods: We searched Medline (Ovid), Embase (Ovid), Cochrane Central Register of Controlled Trials (CENTRAL), CNKI, WanFang Data and VIP from the establishment of databases to July 2022.

Silymarin Protects against Acute Liver Injury Induced by Acetaminophen by Downregulating the Expression and Activity of the CYP2E1 Enzyme.

Previous studies have shown that silymarin protects against various types of drug-induced liver injury, but whether the protective mechanism of silymarin against acetaminophen-induced liver injury is related to the CYP2E1 enzyme remains unclear. In this study, we investigated the effect of silymarin on the activity and expression of CYP2E1 in vitro and in vivo. The results of in vitro studies showed that silymarin not only inhibited the activity of CYP2E1 in human and rat liver microsomes but also reduced the expression of CYP2E1 in HepG2 cells.

Targeted inhibition of FcRn reduces NET formation to ameliorate experimental ulcerative colitis by accelerating ANCA clearance.

Dysregulated immune responses have now been recognized as an essential stimulator of ulcerative colitis (UC). Neutrophil extracellular traps (NET) were reported as the potential factor in sustaining mucosal inflammation in UC. NET formation further induces antineutrophil cytoplasm autoantibodies (ANCA) that serve as a biomarker in determining the severity of UC, which have a long half-life due to neonatal Fc receptor (FcRn)-mediated recycling.

Physiologically based pharmacokinetic modeling of brivaracetam and its interactions with rifampin based on CYP2C19 phenotypes.

Brivaracetam (BRV), a third-generation antiepileptic drug (AED), is primarily metabolized through amidase hydrolysis and CYP2C19-mediated hydroxylation in vivo. This study utilized physiologically based pharmacokinetic (PBPK) modeling to explore the pharmacokinetics of BRV and drug interactions between BRV and rifampin (RIF), a CYP2C19 inducer, based on CYP2C19 genetic polymorphisms. A PBPK model of BRV was developed in the general population and in individuals with different CYP2C19 phenotypes by adjusting catalytic rate constants (k), and the model was validated with observed clinical data.

Changes in target ability of nanoparticles due to protein corona composition and disease state.

Many studies have shown the influence of protein corona (PC) on the active targeting capability of ligand-modified nanoparticles; however, the influence of clinical status on PC composition and targeting capacity is rarely discussed. In this study, when transferrin-modified PEGylated polystyrene nanoparticles (Tf-PNs) is intravenously injected into mice with non-small cell lung cancer (NSCLC) comorbid with type 2 diabetes mellitus (T2DM), more Tf-PNs accumulated in the tumor tissue than in those of NSCLC model mice. This indicated that PC derived from different states of disease changed the active targeting ability of Tf-PNs.

Tanshinone IIA prevents acetaminophen-induced nephrotoxicity through the activation of the Nrf2-Mrp2/4 pathway in mice.

It's known that APAP overdose often leads to hepatotoxicity and nephrotoxicity. In the present study, we investigated the preventative effect of Tan IIA on APAP-induced nephrotoxicity. Mice were orally administrated with Tan IIA (10 or 30 mg/kg/day) for 1 week and subsequently gavaged with 200 mg/kg of APAP.

Physiologically Based Pharmacokinetic Modeling in Pregnant Women Suggests Minor Decrease in Maternal Exposure to Olanzapine.

Pregnancy is accompanied by significant physiological changes that might affect the drug disposition. Olanzapine is prescribed to pregnant women with schizophrenia, while its pharmacokinetics during pregnancy remains unclear. This study aimed to develop a physiologically based pharmacokinetic (PBPK) model of olanzapine in the pregnant population.

Mechanism and Protection of Radiotherapy Induced Sensorineural Hearing Loss for Head and Neck Cancer.

Purpose: Radiotherapy-induced sensorineural hearing loss (RISNHL) is a common adverse effect in patients with head and neck cancer. Given that there are few studies on the pathogenesis of RISNHL at present, we summarized the possible pathogenesis of RISNHL and possible protective measures found at present by referring to relevant literatures.

Methods: We performed a comprehensive literature search in the PubMed database, using keywords "sensorineural hearing loss," "radiotherapy," and "cancer," among others.

Assessment of Health-Related Quality of Life Using EuroQoL-5 Dimension in Populations With Prediabetes, Diabetes, and Normal Glycemic Levels in Southwest China.

This study aimed to describe and compare health-related quality of life (HRQoL) among populations with normal glycemic levels, prediabetes, and diabetes in southwest China and to offer baseline data that can be easily compared to other regions in China or across countries. A quality of life survey based on the EuroQoL-5 Dimension-5 level (EQ-5D-5L) scale was conducted through face-to-face or telephone interviews. A total of 403 respondents with diabetes, 404 with prediabetes, and 398 with normal blood glucose were enrolled in the survey.

Assessing CYP2C8-Mediated Pharmaceutical Excipient-Drug Interaction Potential: A Case Study of Tween 80 and Cremophor EL-35.

Pharmaceutical excipients (PEs) are substances included in drug formulations. Recent studies have revealed that some PEs can affect the activity of metabolic enzymes and drug transporters; however, the effects of PEs on CYP2C8 and its interaction potential with drugs remain unclear. In this study, we evaluated the effects of Tween 80 and EL-35 on CYP2C8 in vitro and further investigated their impacts on the PK of paclitaxel (PTX) in rats after single or multiple doses.

Guideline for the evaluation of prescription appropriateness.

Evaluation of prescriptions is a necessary process of evaluating the appropriateness of clinical drug usage, discovering existing problems, and formulating solutions. There are challenges for professionals within hospital medical departments and for clinicians and pharmacists who have clinical questions relating to inappropriate or abnormal prescriptions as identified by the electronic evaluation system of prescription. Medications are usually used correctly according to the drug instructions or guidelines.

Cost-Effectiveness Analysis of Triple Combination Preparations in the Treatment of Moderate-to-Severe Chronic Obstructive Pulmonary Disease.

This study analyzed the long-term cost-effectiveness of fluticasone/umeclidinium/vilanterol triple combination (FF/UMEC/VI) vs. budesonide/formoterol double combination (BUD/FOR) in the treatment of moderate-to-severe chronic obstructive pulmonary disease (COPD) and provides evidence for COPD treatment decisions. From the perspective of the healthcare system, a Markov model was established that consists of four states-stable period, non-severely deteriorating period, severely deteriorating period, and death-according to real-world COPD progression.

Erratum.

Colon cancer (CC) is the third most common cancer worldwide. Emodin is an anthraquinone-active substance that has the ability to affect tumor progression. Our study aims to explore the effects and the relevant mechanism of emodin on the invasion and migration of CC in vitro and in vivo.

Quantitation of Apremilast in Beagle Dogs Plasma by UPLC-MS-MS and Its Application to Pharmacokinetic Studies.

A sensitive and selective ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS-MS) method for the determination of apremilast in beagle dog plasma has been developed and successfully validated in the current study. Clopidogrel was employed as an internal standard (IS), and liquid-liquid extraction by tert-butylmethyl ether was used for sample preparation. Chromatographic separation was achieved on a UPLC BEH Shield RP18 column (50 mm × 2.

Pipette-tip micro-solid phase extraction based on melamine-foam@polydopamine followed by ultra-high-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry for detection of psychotropic drugs in human serum.

In this work, pipette-tip micro-solid phase extraction (PT-μSPE) which packed by melamine-foam@polydopamine (MF@PDA) coupled with ultra-high-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UHPLC-QTOF) was developed for extraction and determination of psychotropic drugs in serum samples. Considering the operation back pressure, the melamine-foam as carrier material with 3D cross-linked grid structure can provide high permeability and contact surface. MF@PDA was prepared by self-polymerization reaction of dopamine under weak alkaline conditions and characterized by scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX) and X-ray photoelectron spectroscopy (XPS).

Physiologically based pharmacokinetic modeling of tramadol to inform dose adjustment and drug-drug interactions according to CYP2D6 phenotypes.

Objectives: The objective of this study was to establish physiologically based pharmacokinetic (PBPK) models of tramadol and its active metabolite O-desmethyltramadol (M1) and to explore the influence of CYP2D6 gene polymorphism on the pharmacokinetics of tramadol and M1. Furthermore, we used PBPK modeling to prospectively predict the extent of drug-drug interactions (DDIs) in the presence of genetic polymorphisms when tramadol was co-administered with the CYP2D6 inhibitors duloxetine and paroxetine.

Methods: Plasma concentrations of tramadol and M1 were used to adjust the turnover frequency (K ) of CYP2D6 for phenotype populations with different CYP2D6 genotypes.

Dose Adjustment of Quetiapine and Aripiprazole for Pregnant Women Using Physiologically Based Pharmacokinetic Modeling and Simulation.

Background And Objective: Quetiapine and aripiprazole are currently prescribed for pregnant women to treat schizophrenia and bipolar disorder. A dramlatic decline in the plasma concentrations of these two drugs was observed if the doses remained fixed throughout pregnancy. This study aims to develop physiologically based pharmacokinetic (PBPK) models to predict the pharmacokinetics of quetiapine, aripiprazole, and the active aripiprazole metabolite dehydroaripiprazole during pregnancy.

Enhanced Cancer-targeted Drug Delivery Using Precoated Nanoparticles.

While protein coronas (PCs) are an important barrier in the clinical application of nanomedicines, the specific effects of PCs on nanoparticles (NPs) are unclear. Herein, we demonstrated that PCs from clinical sources greatly influenced the active targeting capacities of transferrin-modified NPs (Tf-NPs). Compared to PCs from healthy volunteers, PCs from the plasma of patients with nonsmall cell lung cancer (NSCLC) decreased the A549 uptake of Tf-NPs to a greater degree.

Investigating the Fate of MP1000-LPX by Adding Serum to Transfection Medium.

Background: Cationic liposomes (CLs) based messenger RNA (mRNA) vaccine has been a promising approach for cancer treatment. However, rapid lung accumulation after intraveous injection and significantly decreased transfection efficacy (TE) in serum substantially hamper its application.

Objective: In this study, we attempt to investigate the fate of Mannose-PEG1000-lipoplex (MP1000-LPX) in vivo, a previous reported mRNA vaccine, and potential mechanism in it.

Tanshinone IIA attenuates acetaminophen-induced hepatotoxicity through HOTAIR-Nrf2-MRP2/4 signaling pathway.

Tanshinone IIA (Tan IIA), an active component in S. miltiorrhiza, has been reported to have excellent antioxidant and detoxifying activity. Here, we prove that Tan IIA attenuates acetaminophen-induced hepatotoxicity from a pharmacokinetic perspective.