Inorganic Mercury Pharmacokinetics in Man: A Hybrid Model.

IF 1.3 4区医学 Q4 PHARMACOLOGY & PHARMACY

Xenobiotica Pub Date : 2025-01-10 DOI:10.1080/00498254.2024.2448979

Fred Farris, Ayda Awaness, Joe Su

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引用次数: 0

Abstract

A four-compartment model is presented that simulates inorganic mercury [Hg(II)] pharmacokinetics in blood, tissue, and excreta over a 70 day period. Simulations are validated against data collected from five human subjects, and previously analyzed (Farris, F.F., A. Kaushal, and J.G. Strom. 2008. "Inorganic Mercury Pharmacokinetics in Man: A Two-Compartment Model." Toxicol Environ Chem. 90: 519-533). In the model, two compartments simulate Hg(II) in blood: one for mobile-Hg(II) and the other for immobile-Hg(II). Two corresponding compartments simulate Hg(II) in tissue. Mobile-Hg(II) represents Hg(II) available for transport across cell membranes. Immobile-Hg(II) represents Hg(II) that is not easily transported. Following dosing, blood total-Hg(II) drops rapidly in all subjects. Blood mobile-Hg(II) also drops rapidly with a concomitant rise in blood immobile-Hg(II). For four subjects, immobile-Hg(II) becomes the dominant Hg(II) species in blood by day 4. For subject five, mobile-Hg(II) remains dominant in blood for the study duration. Tissue mobile-Hg(II) declines rapidly for four of the subjects, with a simultaneous rapid rise in tissue immobile-Hg(II). In subject 5, tissue mobile-Hg(II) declines linearly, and immobile-Hg(II) accumulates slowly in tissue. For all subjects, tissue mobile-Hg(II) is the primary source of fecal Hg(II). The major source for Hg(II) excreted into the urine is immobile-Hg(II) from tissue.

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来源期刊

Xenobiotica 医学-毒理学

CiteScore

3.80

自引率

5.60%

发文量

审稿时长

2 months

期刊介绍： Xenobiotica covers seven main areas, including:General Xenobiochemistry, including in vitro studies concerned with the metabolism, disposition and excretion of drugs, and other xenobiotics, as well as the structure, function and regulation of associated enzymesClinical Pharmacokinetics and Metabolism, covering the pharmacokinetics and absorption, distribution, metabolism and excretion of drugs and other xenobiotics in manAnimal Pharmacokinetics and Metabolism, covering the pharmacokinetics, and absorption, distribution, metabolism and excretion of drugs and other xenobiotics in animalsPharmacogenetics, defined as the identification and functional characterisation of polymorphic genes that encode xenobiotic metabolising enzymes and transporters that may result in altered enzymatic, cellular and clinical responses to xenobioticsMolecular Toxicology, concerning the mechanisms of toxicity and the study of toxicology of xenobiotics at the molecular levelXenobiotic Transporters, concerned with all aspects of the carrier proteins involved in the movement of xenobiotics into and out of cells, and their impact on pharmacokinetic behaviour in animals and manTopics in Xenobiochemistry, in the form of reviews and commentaries are primarily intended to be a critical analysis of the issue, wherein the author offers opinions on the relevance of data or of a particular experimental approach or methodology