A physiologically-based pharmacokinetic model for the antibiotic ertapenem
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Department of Mathematics & Statistics, East Tennessee State University, Johnson City, TN, 37614
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Department of Mathematics and Computer Science, Meredith College, Raleigh, NC, 27607
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Department of Mathematics & Computer Science, Meredith College, Raleigh, NC, 27607
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Received:
01 May 2015
Accepted:
29 June 2018
Published:
01 October 2015
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MSC :
Primary: 92C45; Secondary: 34A35, 65L09.
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Ertapenem is an antibiotic commonly used to treat a broad spectrum of infections, which is part of a broader class of antibiotics called carbapenem. Unlike other carbapenems, ertapenem has a longer half-life and thus only has to be administered once a day. A physiologically-based pharmacokinetic (PBPK) model was developed to investigate the uptake, distribution, and elimination of ertapenem following a single one gram dose. PBPK modeling incorporates known physiological parameters such as body weight, organ volumes, and blood flow rates in particular tissues. Furthermore, ertapenem is highly bound in human blood plasma; therefore, nonlinear binding is incorporated in the model since only the free portion of the drug can saturate tissues and, hence, is the only portion of the drug considered to be medicinally effective. Parameters in the model were estimated using a least squares inverse problem formulation with published data for blood concentrations of ertapenem for normal height, normal weight males. Finally, an uncertainty analysis of the parameter estimation and model predictions is presented.
Citation: Michele L. Joyner, Cammey C. Manning, Whitney Forbes, Michelle Maiden, Ariel N. Nikas. A physiologically-based pharmacokinetic model for the antibiotic ertapenem[J]. Mathematical Biosciences and Engineering, 2016, 13(1): 119-133. doi: 10.3934/mbe.2016.13.119
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Abstract
Ertapenem is an antibiotic commonly used to treat a broad spectrum of infections, which is part of a broader class of antibiotics called carbapenem. Unlike other carbapenems, ertapenem has a longer half-life and thus only has to be administered once a day. A physiologically-based pharmacokinetic (PBPK) model was developed to investigate the uptake, distribution, and elimination of ertapenem following a single one gram dose. PBPK modeling incorporates known physiological parameters such as body weight, organ volumes, and blood flow rates in particular tissues. Furthermore, ertapenem is highly bound in human blood plasma; therefore, nonlinear binding is incorporated in the model since only the free portion of the drug can saturate tissues and, hence, is the only portion of the drug considered to be medicinally effective. Parameters in the model were estimated using a least squares inverse problem formulation with published data for blood concentrations of ertapenem for normal height, normal weight males. Finally, an uncertainty analysis of the parameter estimation and model predictions is presented.
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