Development and validation of a sensitive and fast bioanalytical LC-MS/MS assay for the quantitation of venetoclax and azacitidine in Rat Plasma: Application to pharmacokinetic study.

The combination of venetoclax plus azacitidine (VTX-AZA) is FDA-approved to treat patients with acute myeloid leukemia (AML) aged ≥75 years and has become the standard of care for AML patients. However, the literature has not reported an analytical method for determining VTX-AZA in plasma samples. Therefore, developing an accurate and sensitive bioanalytical assay to quantify VTX-AZA in plasma is important.

Fenofibrate as an Adjunct Therapy for Ulcerative Colitis: Targeting Inflammation via SIRT1, NLRP3, and AMPK Pathways: A Randomized Controlled Pilot Study.

Background: Ulcerative colitis (UC) is an idiopathic chronic inflammation of colonic and rectal mucosa. The peroxisome proliferator-activated receptor α (PPARα) has been identified as having protective effects in UC.

Aim: The study aimed to investigate the efficacy of fenofibrate, a PPARα agonist, in UC.

A Simple Eco-Friendly HPLC-PDA Method for the Simultaneous Determination of Paclitaxel and Seliciclib in Plasma Samples for Assessing Their Pharmacodynamics and Pharmacokinetics in Combination Therapy for Uterine Sarcoma.

: Uterine sarcoma, a rare cancer originating in the smooth muscle of the uterus, exhibits high rates of recurrence and metastasis. It represents one of the most challenging types of cancer due to its chemorefractory nature, showing little response to conventional chemotherapy methods and displaying a relative survival rate of 30-40%. A potentially promising approach for treating uterine sarcoma involves combination therapy with paclitaxel (PAC), a microtubule-targeting agent, and seliciclib (SEL), a cyclin-dependent kinase inhibitor.

A randomized controlled trial comparing tacrolimus versus hydrocortisone for the treatment of atopic dermatitis in children: new perspectives on interferon gamma-induced protein and growth-related oncogene-α.

Introduction: Atopic dermatitis (AD) is a type of chronic inflammatory disorder that affects children.

Aim: To investigate whether hydrocortisone or tacrolimus could be more effective for treating AD in children.

Patients And Methods: This clinical randomized investigation included 100 children with AD who met the eligibility criteria.

A guide to developing population files for physiologically-based pharmacokinetic modeling in the Simcyp Simulator.

The Simcyp Simulator is a software platform widely used in the pharmaceutical industry to conduct stochastic physiologically-based pharmacokinetic (PBPK) modeling. This approach has the advantage of combining routinely generated in vitro data on drugs and drug products with knowledge of biology and physiology parameters to predict a priori potential pharmacokinetic changes in absorption, distribution, metabolism, and excretion for populations of interest. Combining such information with pharmacodynamic knowledge of drugs enables planning for potential dosage adjustment when clinical studies are feasible.

Complementarity of two proteomic data analysis tools in the identification of drug-metabolising enzymes and transporters in human liver.

Several software packages are available for the analysis of proteomic LC-MS/MS data, including commercial ( Mascot/Progenesis LC-MS) and open access software ( MaxQuant). In this study, Progenesis and MaxQuant were used to analyse the same data set from human liver microsomes ( = 23). Comparison focussed on the total number of peptides and proteins identified by the two packages.

Evaluating the safety and efficacy of the leukotriene receptor antagonist montelukast as adjuvant therapy in obese patients with type 2 diabetes mellitus: A double-blind, randomized, placebo-controlled trial.

Type 2 diabetes mellitus (T2DM) is common with obesity. Metformin is a first-line therapy for this condition. However, it has only a minor impact on weight loss in some patients.

Altered Bioavailability and Pharmacokinetics in Crohn's Disease: Capturing Systems Parameters for PBPK to Assist with Predicting the Fate of Orally Administered Drugs.

Backgrond And Objective: Crohn's disease (CD) is a chronic inflammatory bowel disease that affects a wide age range. Hence, CD patients receive a variety of drugs over their life beyond those used for CD itself. The changes to the integrity of the intestine and its drug metabolising enzymes and transporters (DMETs) can alter the oral bioavailability of drugs.

Quantitative Assessment of the Impact of Crohn's Disease on Protein Abundance of Human Intestinal Drug-Metabolising Enzymes and Transporters.

Crohn's disease affects the mucosal layer of the intestine, predominantly ileum and colon segments, with the potential to affect the expression of intestinal enzymes and transporters, and consequently, oral drug bioavailability. We carried out a quantitative proteomic analysis of inflamed and non-inflamed ileum and colon tissues from Crohn's disease patients and healthy donors. Homogenates from samples in each group were pooled and protein abundance determined by liquid chromatography-mass spectrometry (LC-MS).

Proteomic quantification of perturbation to pharmacokinetic target proteins in liver disease.

Model-based assessment of drug pharmacokinetics in liver disease requires quantification of abundance and disease-related changes in hepatic enzymes and transporters. This study aimed to assess performance of three label-free methods [high N (HiN), intensity-based absolute quantification (iBAQ) and total protein approach (TPA)] against QconCAT-based targeted data in healthy and diseased (cancer and cirrhosis) liver tissue. Measurements were compared across methods and disease-to-control ratios provided a 'disease perturbation factor' (DPF) for each protein.

A family of QconCATs (Quantification conCATemers) for the quantification of human pharmacological target proteins.

We have developed a family of QconCAT standards for the absolute quantification of pharmacological target proteins in a variety of human tissues. The QconCATs consist of concatenated proteotypic peptides, are designed in silico, and expressed in E. coli in media enriched with [C] arginine and [C] lysine to generate stable isotope-labeled multiplexed absolute quantification standards.

Label-Free but Still Constrained: Assessment of Global Proteomic Strategies for the Quantification of Hepatic Enzymes and Transporters.

Building and refining pharmacology models require "system" data derived from tissues and in vitro systems analyzed by quantitative proteomics. Label-free global proteomics offers a wide scope of analysis, allowing simultaneous quantification of thousands of proteins per sample. The data generated from such analysis offer comprehensive protein expression profiles that can address existing gaps in models.

Mass spectrometry-based abundance atlas of ABC transporters in human liver, gut, kidney, brain and skin.

ABC transporters (ATP-binding cassette transporter) traffic drugs and their metabolites across membranes, making ABC transporter expression levels a key factor regulating local drug concentrations in different tissues and individuals. Yet, quantification of ABC transporters remains challenging because they are large and low-abundance transmembrane proteins. Here, we analysed 200 samples of crude and membrane-enriched fractions from human liver, kidney, intestine, brain microvessels and skin, by label-free quantitative mass spectrometry.

Quantitative mass spectrometry-based proteomics in the era of model-informed drug development: Applications in translational pharmacology and recommendations for best practice.

Quantitative translation of the fate and action of a drug in the body is facilitated by models that allow extrapolation of in vitro measurements (such as the rate of metabolism, active transport across membranes, inhibition of enzymes and receptor occupancy) to in vivo consequences (intensity and duration of drug effects). These models use various physiological parameters, including data that describe the expression levels of pharmacologically relevant enzymes, transporters and receptors in tissues and in vitro systems. Immunoquantification approaches have traditionally been used to determine protein expression levels, generally providing relative quantification data with compromised selectivity and reproducibility.

Physical and chemical screening of honey samples available in the Saudi market: An important aspect in the authentication process and quality assessment.

Honey is becoming accepted as a reputable and effective therapeutic agent by practitioners of conventional medicine and by the general public. It has many biological activities and has been effectively used in the treatment of many diseases, e.g.