Trial reportBMC clinical pharmacology2007
Heterogeneity of human adipose blood flow.
Trial report in BMC clinical pharmacology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed.
- Context-sensitive decrement times for inhaled anesthetics in obese patients explored with Gas Man®.Journal of clinical monitoring and computing · 2021Article
- A marijuana-drug interaction primer: Precipitants, pharmacology, and pharmacokinetics.Pharmacology & therapeutics · 2019Review
- PKQuest: PBPK modeling of highly lipid soluble and extracellular solutes.ADMET & DMPK · 2019Article
- Computational Model of Drug-Coated Balloon Delivery in a Patient-Specific Arterial Vessel with Heterogeneous Tissue Composition.Cardiovascular engineering and technology · 2016Article
- Quantitative relationship between the octanol/water partition coefficient and the diffusion limitation of the exchange between adipose and blood.BMC clinical pharmacology · 2010Article
- PKQuest_Java: free, interactive physiologically based pharmacokinetic software package and tutorial.BMC research notes · 2009Article
- Development of PBPK model of molinate and molinate sulfoxide in rats and humans.Regulatory toxicology and pharmacology : RTP · 2009Article
- Physiological models of body composition and human obesity.Nutrition & metabolism · 2007Article
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1 author.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundThe long time pharmacokinetics of highly lipid soluble compounds is dominated by blood-adipose tissue exchange and depends on the magnitude and heterogeneity of adipose blood flow. Because the adipose tissue is an infinite sink at short times (hours), the kinetics must be followed for days in order to determine if the adipose perfusion is heterogeneous. The purpose of this paper is to quantitate human adipose blood flow heterogeneity and determine its importance for human pharmacokinetics.
methodsThe heterogeneity was determined using a physiologically based pharmacokinetic model (PBPK) to describe the 6 day volatile anesthetic data previously published by Yasuda et. al. The analysis uses the freely available software PKQuest and incorporates perfusion-ventilation mismatch and time dependent parameters that varied from the anesthetized to the ambulatory period. This heterogeneous adipose perfusion PBPK model was then tested by applying it to the previously published cannabidiol data of Ohlsson et. al. and the cannabinol data of Johansson et. al.
resultsThe volatile anesthetic kinetics at early times have only a weak dependence on adipose blood flow while at long times the pharmacokinetics are dominated by the adipose flow and are independent of muscle blood flow. At least 2 adipose compartments with different perfusion rates (0.074 and 0.014 l/kg/min) were needed to describe the anesthetic data. This heterogeneous adipose PBPK model also provided a good fit to the cannabinol data.
conclusionHuman adipose blood flow is markedly heterogeneous, varying by at least 5 fold. This heterogeneity significantly influences the long time pharmacokinetics of the volatile anesthetics and tetrahydrocannabinol. In contrast, using this same PBPK model it can be shown that the long time pharmacokinetics of the persistent lipophilic compounds (dioxins, PCBs) do not depend on adipose blood flow. The ability of the same PBPK model to describe both the anesthetic and cannabinol kinetics provides direct qualitative evidence that their kinetics are flow limited and that there is no significant adipose tissue diffusion limitation.
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