Definition of a Physiologic Pharmacokinetic Model of Cutaneous Drug Distribution Using the Isolated Perfused Porcine Skin Flap

Williams, Patrick L.; Riviere, Jim E.

doi:10.1002/jps.2600780708

Cited by 35 publications

(8 citation statements)

References 14 publications

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“…Data was analyzed based on a pharmacokinetic model previously optimized for platinum chemotherapeutic compound distribution in infused skin, a compound class also marked by irreversible tissue binding. 24 COOH-QD 621 (negative charge) uptake into skin was 2-3 fold greater than for PEG-QD621 (neutral). This is consistent with increased tissue distribution of negative charged QD discussed above.…”

Section: Quantum Dotsmentioning

confidence: 90%

“…Significantly, there was no radioactivity detected in urine and feces collected every 24 h for 5 days. Similarly, Qiang et al 9 studied 0.5 mg/kg intravenous C 60 (OH) 24 disposition in mice and demonstrated organ accumulation, as well as only 50% excretion after 3 days, with over 50% excreted in feces and only 4% in urine. Bone showed a pattern of continued accumulation.…”

Section: Carbon-based Nanomaterials-fullerenes (C 60 ) and Nanotubesmentioning

confidence: 94%

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Pharmacokinetics of nanomaterials: an overview of carbon nanotubes, fullerenes and quantum dots

Riviere

2008

WIREs Nanomed Nanobiotechnol

120

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A full understanding of the pharmacokinetic parameters describing nanomaterial disposition in the body would greatly facilitate development of a firm foundation upon which risk assessment could be based. This review focuses on the disposition of carbon based fullerenes and nanotubes, as well as quantum dots (QD) after parenteral administration to primarily rodents. The common theme across all particle types is that a major determinant of nanomaterial disposition is the degree of interaction with the reticuloendothelial (RE) cell system. Small water-soluble particles evading this system may be excreted by the kidney. Larger particles and those with the proper surface charge may get targeted to RE cells in the liver, spleen and other organs. Most nanomaterial kinetics are characterized by relatively short blood half-lives reflecting tissue extraction and not by clearance from the body. In fact, another common attribute to nanomaterial kinetics is retention of particles in the body. Finally, unlike many small organic drugs, nanomaterials may preferentially be trafficked in the body via the lymphatic system that has obvious immunological implications . T he technological and biomedical advancements inherent to the application of nanomaterials are becoming increasingly evident. In the field of medical applications, a thorough understanding of their pharmacokinetic properties is crucial for their safe and efficacious application. From the perspective of characterizing potential adverse effects, these data are also required for quantitative risk assessments to define the toxicology of the material. Pharmacokinetics is defined as the science of quantifying the rate and extent of the absorption, distribution, metabolism and elimination (ADME) of chemicals and drugs in the body using mathematical modeling approaches. The aim of pharmacokinetics is to relate drug dose or chemical exposure to biological effect. Pharmacokinetics has developed distinct sets of models and parameters which have been useful to describe and predict drug and chemical disposition, and also have specific

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Section: Quantum Dotsmentioning

confidence: 90%

Section: Carbon-based Nanomaterials-fullerenes (C 60 ) and Nanotubesmentioning

confidence: 94%

Pharmacokinetics of nanomaterials: an overview of carbon nanotubes, fullerenes and quantum dots

Riviere

2008

WIREs Nanomed Nanobiotechnol

120

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“…First possibility, they can distribute to compartment 3 and or they leave compartment two via venous efflux. Here, also we have assumed that the uptake depends on NP concentration in compartment two and it does not depend on perforate blood flow [4] [32]. For the first compartment, we can easily obtain the following equality: where we consider Γ as the beginning time of washout phase that is zero during dosing phase [32].…”

Section: A Simple Three Compartmental Model Example For Np Distributionmentioning

confidence: 99%

Global Sensitivity Analysis in Physiological Systems

Azizi¹,

Mugabi²

2020

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Pharmacokinetic models are mathematical models which provide insights into the interaction of chemicals with biological processes. During recent decades, these models have become central of attention in industry that caused to do a lot of efforts to make them more accurate. Current work studies the process of drug and nanoparticle (NPs) distribution throughout the body which consists of a system of ordinary differential equations. We use a tri-compartmental model to study the perfusion of NPs in tissues and a six-compartmental model to study drug distribution in different body organs. We have performed global sensitivity analysis by LHS Monte Carlo method using PRCC. We identify the key parameters that contribute most significantly to the absorption and distribution of drugs and NPs in different organs in body.

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“…This, in turn, requires that k13 be a function of the input flux and the net flux from compartment 1 to compartment 2 (non-vascular skin). A detailed description of this model is given in Williams & Riviere (1989). The differential equations are given by Equations 45-47:…”

Section: (44)mentioning

confidence: 99%

Structural identiflability of pharmacokinetic models‐compartments and experimental design

1990

Vet Pharm & Therapeutics

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Definition of a Physiologic Pharmacokinetic Model of Cutaneous Drug Distribution Using the Isolated Perfused Porcine Skin Flap

Cited by 35 publications

References 14 publications

Pharmacokinetics of nanomaterials: an overview of carbon nanotubes, fullerenes and quantum dots

Pharmacokinetics of nanomaterials: an overview of carbon nanotubes, fullerenes and quantum dots

Global Sensitivity Analysis in Physiological Systems

Structural identiflability of pharmacokinetic models‐compartments and experimental design

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