Gamma variate fits to pharmacokinetic data

Pfeffer, Morris

doi:10.1007/bf03189934

Cited by 2 publications

(3 citation statements)

References 12 publications

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“…Pharmacokinetic data and fits with a gamma variate model [ 24 , 30 ] (online methods and Supplementary Fig. S2 ) are shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Aptamer concentration data ( C ) as a function of time after injection ( t ) were plotted and then fit [ 23 ] with equation 2 reflecting the sum of two gamma variates [ 24 ]: \documentclass{aastex}\usepackage{amsbsy}\usepackage{amsfonts}\usepackage{amssymb}\usepackage{bm}\usepackage{mathrsfs}\usepackage{pifont}\usepackage{stmaryrd}\usepackage{textcomp}\usepackage{portland, xspace}\usepackage{amsmath, amsxtra}\pagestyle{empty}\DeclareMathSizes{10}{9}{7}{6}\begin{document} \begin{align*} C (t) = k_ {1} \left(\frac {{\rm ln} 2} {b_ {1}} t \right) ^ \frac {{\rm ln} \ 2} {a_ {1}} e^ {- \frac {{\rm ln} \ 2} {b_ {1}} t} + k_ {2} \left( \frac {{\rm ln} 2} {b_ {2}} t \right) ^ \frac {{\rm ln} \ 2} {a_ {2}} e^ {- \frac {{\rm ln} \ 2} {b_ {2}} t} \tag {2} \end{align*} \end{document} …”

Section: Methodsmentioning

confidence: 99%

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Quantitative PCR Analysis of DNA Aptamer Pharmacokinetics in Mice

Perschbacher

Smestad

Peters

et al. 2015

Nucleic Acid Therapeutics

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DNA aptamer oligonucleotides and their protein conjugates show promise as therapeutics in animal models of diseases such as multiple sclerosis. These molecules are large and highly charged, raising questions about their biodistribution and pharmacokinetics in mammals. Here we exploit the power of quantitative polymerase chain reaction to accurately quantitate the tissue distribution of 40-nucleotide DNA aptamers and their streptavidin conjugates after intraperitoneal injection in mice. We show remarkably rapid distribution to peripheral tissues including the central nervous system. Modeling of tissue distribution data reveals the importance of DNA aptamer sequence, 3′ modification, and protein conjugation in enhancing tissue exposure. These data help to interpret the previously observed effectiveness of aptamer conjugates, as opposed to free aptamers, in stimulating central nervous system remyelination in a mouse model of multiple sclerosis.

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“…Pharmacokinetic data and fits with a gamma variate model [ 24 , 30 ] (online methods and Supplementary Fig. S2 ) are shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Quantitative PCR Analysis of DNA Aptamer Pharmacokinetics in Mice

Perschbacher

Smestad

Peters

et al. 2015

Nucleic Acid Therapeutics

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show abstract

“…Diffusion is limited because molecules are not able to move in all directions. This model can be used to interpret the pharmacokinetics of calcium [132] or the transport and dispersion of tracers in the circulatory system [133] and provides theoretical justification for the above-mentioned empirical potency and gamma functions [114,[134][135][136].…”

Section: Fractal Modelsmentioning

confidence: 99%

Drug Tissue Distribution: Study Methods and Therapeutic Implications

Lanao¹,

Fraile²

2005

CPD

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Current interest in studies on tissue distribution stems from the limited capacity to predict tissue concentrations and the pharmacological response from plasma drug levels, and from the limitations - both methodological and deontological- involved in doing so, especially in humans. In this review we carry out a comparative analysis of the methods used for studying tissue distribution, placing special focus on recently developed non-invasive methods for the research of tissue distribution in humans, such as positron emission tomography and nuclear magnetic resonance spectroscopy. We describe the strategies of tissue distribution pharmacokinetic analysis that have evolved from analysis based on compartment and physiological models to analyses based on spatial and fractal models and, mainly, pharmacokinetic-pharmacodynamic models. Model-independent analysis based on the use of mean transit times or deconvolution strategies has become a good alternative for the pharmacokinetic analysis of tissue distribution. The need to increase the selectivity of many drugs justifies the desire to gain further insight into the design of new analogues prodrugs and carrier systems that will guarantee the specific delivery of a given drug to a particular organ or tissue, optimising the response. In silico models for drug distribution have become a helpful tool in drug discovery and development. The therapeutic implications of drug tissue distribution are also analysed, special reference being made to antiretroviral therapy and antitumoural gene therapy, among others.

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Gamma variate fits to pharmacokinetic data

Cited by 2 publications

References 12 publications

Quantitative PCR Analysis of DNA Aptamer Pharmacokinetics in Mice

Quantitative PCR Analysis of DNA Aptamer Pharmacokinetics in Mice

Drug Tissue Distribution: Study Methods and Therapeutic Implications

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