ArticleBMC clinical pharmacology2010
Quantitative relationship between the octanol/water partition coefficient and the diffusion limitation of the exchange between adipose and blood.
Article in BMC clinical pharmacology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.
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Who cites it
9 citing papers in PubMed, 1 synthesis or guideline pooled it, 58 citations in OpenAlex.
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- Urinary levels of dimethoate, bisphenol A and benzo[a]pyrene in first-year students of Hohai University from different geographical regions.BMC public health · 2021Article
- Adipose to serum ratio and mixtures of persistent organic pollutants in relation to endometriosis: Findings from the ENDO Study.Environmental research · 2021Article
- Effects of Aryl Hydrocarbon Receptor Deficiency on PCB-77-Induced Impairment of Glucose Homeostasis during Weight Loss in Male and Female Obese Mice.Environmental health perspectives · 2019Article
- PKQuest: PBPK modeling of highly lipid soluble and extracellular solutes.ADMET & DMPK · 2019Article
- Adipose Tissue as a Site of Toxin Accumulation.Comprehensive Physiology · 2017Review
- Ratio of cord to maternal serum PCB concentrations in relation to their congener-specific physicochemical properties.International journal of hygiene and environmental health · 2015Article
- Toxicological function of adipose tissue: focus on persistent organic pollutants.Environmental health perspectives · 2013Review
- A systems approach for tumor pharmacokinetics.PloS one · 2011Article
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1 author at 1 institution in 1 country.
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Abstract
backgroundThe goal of physiologically based pharmacokinetics (PBPK) is to predict drug kinetics from an understanding of the organ/blood exchange. The standard approach is to assume that the organ is "flow limited" which means that the venous blood leaving the organ equilibrates with the well-stirred tissue compartment. Although this assumption is valid for most solutes, it has been shown to be incorrect for several very highly fat soluble compounds which appear to be "diffusion limited". This paper describes the physical basis of this adipose diffusion limitation and its quantitative dependence on the blood/water (Kbld-wat) and octanol/water (Kow) partition coefficient.
methodsExperimental measurements of the time dependent rat blood and adipose concentration following either intravenous or oral input were used to estimate the "apparent" adipose perfusion rate (FA) assuming that the tissue is flow limited. It is shown that the ratio of FA to the anatomic perfusion rate (F) provides a measure of the diffusion limitation. A quantitative relationship between this diffusion limitation and Kbld-wat and Kow is derived. This analysis was applied to previously published data, including the Oberg et. al. measurements of the rat plasma and adipose tissue concentration following an oral dose of a mixture of 13 different polychlorinated biphenyls.
resultsSolutes become diffusion limited at values of log Kow greater than about 5.6, with the adipose-blood exchange rate reduced by a factor of about 30 for a solute with a log Kow of 7.36. Quantitatively, a plot of FA/F versus Kow is well described assuming an adipose permeability-surface area product (PS) of 750/min. This PS corresponds to a 0.14 micron aqueous layer separating the well-stirred blood from the adipose lipid. This is approximately equal to the thickness of the rat adipose capillary endothelium.
conclusionsThese results can be used to quantitate the adipose-blood diffusion limitation as a function of Kow. This is especially important for the highly fat soluble persistent organic chemicals (e.g. polychlorinated biphenyls, dioxins) whose pharmacokinetics are primarily determined by the adipose-blood exchange kinetics.
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