The pharmacokinetics of Vaccinium myrtillus anthocyanosides (VMA) have been investigated in male rats. After intravenous administration anthocyanosides undergo a rapid body distribution and their disappearance from the blood is suitably fit...

The pharmacokinetics of Vaccinium myrtillus anthocyanosides (VMA) have been investigated in male rats. After intravenous administration anthocyanosides undergo a rapid body distribution and their disappearance from the blood is suitably fit...

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**Abstract:** This research proposes a novel multi-scale simulation framework for predicting pharmacokinetic (PK) parameters within virtual human microcirculation networks. Traditional PK modeling often simplifies vascular geometry and blood flow dynamics, leading to inaccurate predictions. Our framework integrates computational fluid dynamics (CFD) at the microvascular level with physiologically-based pharmacokinetic (PBPK) models to simulate drug distribution, metabolism, and excretion with unprecedented detail. The system employs a dynamically updating network of virtual capillaries constructed from patient-specific MRI data, coupled with a physics-informed neural network (PINN) to infer drug concentration profiles over time.

**Abstract:** This paper investigates a novel approach to predicting drug-metabolism enzyme interactions using Hyperdimensional Graph Neural Networks (HGNNs). Leveraging the inherent complexity of pharmacokinetic pathways and inter-enzymatic relationships, our model encapsulates drug structures, enzyme sequences, and known interaction data into high-dimensional hypervectors, facilitating the identification of intricate patterns missed by traditional machine learning methods. The proposed HGNN architecture, incorporating a layered hyperdimensional representation and graph convolution operations, demonstrates significantly improved predictive accuracy and interpretability for personalized pharmacokinetic modeling, paving the way for enhanced drug efficacy and safety profiles.

**Abstract:** Current pharmacokinetic (PK) modeling relies on compartmental models and empirical observations, often failing to accurately predict drug behavior *in vivo*. This research introduces a novel approach leveraging hyperdimensional encoding (HDE) coupled with graph neural networks (GNNs) to represent molecular transport pathways within cellular membranes and extracellular spaces. By transforming pathway complexity into high-dimensional vector spaces and utilizing GNNs to analyze pathway interactions, we achieve a 10x improvement in PK prediction accuracy compared to traditional methods, enabling personalized drug dosing strategies and accelerated drug development.

Acyl glucuronides are common metabolites of carboxylic acids. They can be reactive and cause adverse events. The acyl glucuronide metabolite of delta-9-tetrahydrocannabinol (THC) is abundant in humans after THC consumption but acyl glucuronide formation from the cannabidiol (CBD) metabolite 7-carboxy-cannabidiol (7-COOH-CBD) has not been previously described. Here, we identified and characterized both acyl and phenolic glucuronides of 7-COOH-CBD formed in human liver, kidney, and intestinal microsomes. The 7-COOH-CBD-acyl-glucuronide was mostly formed by UGT1A1 and UGT1A3, while the 7-COOH-CBD-phenolic-glucuronide was formed by UGT1A9. 7-COOH-CBD-acyl-glucuronide formation was also detected in vivo in mice. 7-COOH-CBD-acyl-glucuronide showed extensive acyl migration while 11-COOH-THC-glucuronide did not. Human serum albumin enhanced migration, while liver fatty acid binding protein (FABP1) protected against 7-COOH-CBD-acyl-glucuronide migration. When corrected for unbound fraction, FABP1 increased 7-COOH-CBD glucuronidation efficiency. These findings suggest that 7-COOH-CBD-acyl-glucuronide is a metabolite of CBD in humans and may play a role in CBD related liver toxicity.

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Glimepiride (Hoe 490, CAS 93479-97-1), a novel sulfonylurea antidiabetic agent, was studied for the cause of sex-related difference in the elimination clearance of the unchanged drug in rats. After intravenous and oral administration, the s...

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Glimepiride (Hoe 490, CAS 93479-97-1), a novel sulfonylurea antidiabetic agent, was studied for the cause of sex-related difference in the elimination clearance of the unchanged drug in rats. After intravenous and oral administration, the s...

North America Pharmacokinetics And Pharmacodynamics Market is projected to register a CAGR of 7.9% to reach USD 1.49 billion by the end of 2035, North America Pharmacokinetics And Pharmacodynamics Mar...

The pharmacokinetics of ethyl-apovincaminate (vinpocetine, Cavinton), a new vincamine derivative has been studied in volunteers after p.o. and i.v. administration. The concentration of the drug was determined by mass-fragmentography in huma...

Abstract. Insomnia is a serious public health concern. As the widely prescribed hypnotics that positively modulate gamma-aminobutyric acid (GABA)A receptor

The pharmacokinetics of ethyl-apovincaminate (vinpocetine, Cavinton), a new vincamine derivative has been studied in volunteers after p.o. and i.v. administration. The concentration of the drug was determined by mass-fragmentography in huma...