Modeling Ertapenem: the impact of body mass index on distribution of the antibiotic in the body

Michele L. Joyner; Cammey Cole Manning; Whitney Forbes; Valerie Bobola; William Frazier; Michele L. Joyner; Cammey Cole Manning; Whitney Forbes; Valerie Bobola; William Frazier

doi:10.3934/mbe.2019034

Mathematical Biosciences and Engineering

2019, Volume 16, Issue 2: 713-726. doi: 10.3934/mbe.2019034

Previous Article Next Article

Research article

Modeling Ertapenem: the impact of body mass index on distribution of the antibiotic in the body

1.
Department of Mathematics & Statistics, East Tennessee State University, Johnson City, TN, 37614, USA
2.
Department of Mathematics & Computer Science, Meredith College, Raleigh, NC, 27607, USA
3.
Department of Industrial and Systems Engineering, University of Tennessee, Knoxville, TN, 37996, USA

Received: 04 May 2018 Accepted: 02 November 2018 Published: 15 January 2019

Ertapenem is an antibiotic commonly used to treat a broad spectrum of infections and is part of a broader class of antibiotics called carbapenems. Unlike other carbapenems, ertapenem has a longer half-life and thus only has to be administered once a day. Previously, a physiologically-based pharmacokinetic (PBPK) model was developed to investigate the uptake, distribution, and elimination of ertapenem following a single one gram dose in normal height, normal weight males. Due to the absorption properties of ertapenem, the amount of fat in the body can influence how the drug binds, how quickly the drug passes through the body, and thus how effective the drug might be. Thus, we have revised the model so that it is applicable to males and females of differing body mass index (BMI). Simulations were performed to consider the distribution of the antibiotic in males and females with varying body mass indexes. These results could help to determine if there is a need for altered dosing regimens in the future.
- Ertapenem,
- physiologically based pharmacokinetic model (PBPK),
- Body Mass Index (BMI),
- Dosage,
- AUC,
- peak concentration
Citation: Michele L. Joyner, Cammey Cole Manning, Whitney Forbes, Valerie Bobola, William Frazier. Modeling Ertapenem: the impact of body mass index on distribution of the antibiotic in the body[J]. Mathematical Biosciences and Engineering, 2019, 16(2): 713-726. doi: 10.3934/mbe.2019034

Related Papers:

Abstract

Ertapenem is an antibiotic commonly used to treat a broad spectrum of infections and is part of a broader class of antibiotics called carbapenems. Unlike other carbapenems, ertapenem has a longer half-life and thus only has to be administered once a day. Previously, a physiologically-based pharmacokinetic (PBPK) model was developed to investigate the uptake, distribution, and elimination of ertapenem following a single one gram dose in normal height, normal weight males. Due to the absorption properties of ertapenem, the amount of fat in the body can influence how the drug binds, how quickly the drug passes through the body, and thus how effective the drug might be. Thus, we have revised the model so that it is applicable to males and females of differing body mass index (BMI). Simulations were performed to consider the distribution of the antibiotic in males and females with varying body mass indexes. These results could help to determine if there is a need for altered dosing regimens in the future.

References

[1]	H. T. Banks, S. Hu and W. C. Thompson, Modeling and Inverse Problems in the Presence of Uncertainty, SCRC Press, Boca Raton, Fl, 2014.
[2]	H. J. Clewell III, M. B. Reddy, T. Lave and M. E. Andersen, Physiologically based pharmacokinetic modeling, in Preclinical Development Handbook: ADME Biopharmaceutical Properties (ed. S. C. Gad), Wiley-Interscience, John Wiley & Sons, Inc., (2008), 1167–1127.
[3]	G. de Simone, R. B. Devereux, S. R. Daniels, G. Mureddu, M. J. Roman, T. R. Kimball, R. Greco, S. Witt and F. Contaldo, Stroke volume and cardiac output in normotensive children and adults: assessment of relations with body size and impact of overweight, Circulation, 95 (1997), 1837– 1843.
[4]	P. Deeurenberg, J. A. Weststrate and J. C. Seidell, Body mass index as a measure of body fatness: age- and sex-specific prediction formulas, Br. J. Nutr., 65 (1991), 105–114.
[5]	P. Fuster-Parra, M. Bennasar-Veny, P. Tauler, A. Ya˜nez, A. A. L´opez-Gonz´alez and A. Aguil´o, A comparison between multiple regression models and CUN-BAE equation to predict body fat in adults, PLoS ONE, 10 (2015), 1–13.
[6]	P. C. Fuchs, A. L. Barry and S. D. Brown, In vitro activities of ertapenem (mk-0826) against clinical bacterial isolates from 11 north american medical centers, Antimicrob. Agents Ch., 45 (2001), 1915–1918.
[7]	M. L. Joyner, C. C. Manning, W. Forbes, M. Maiden and A. N. Nikas, A physiologically based pharmacokinetic model for the antibiotic ertapenem, Math. Biosci. Eng., 13 (2016), 119–133.
[8]	W. J. Jusko, Pharmacokinetics of capacity-limited systems, J. Clin. Pharmacol., 29 (1989), 488– 493.
[9]	H. Kvist, B. Chowdhury, U. Grangår, U. Tylen and L. Sjöström, Total and visceral adipose tissue volumes derived from measurements with computed tomography in adult men and women: predictive equations, Am. J. Clin. Nutr., 48 (1988), 1351–1361.
[10]	A. K. Majumdar, D. G. Musson, K. L. Birk, C. J. Kitchen, S. Holland, J. McCrea, G. Mistry, M. Hesney, L. Xi, S. X. Li, R. Haesen, R. A. Blum, R. L. Lins, H. Greenberg, S.Waldman, P. Deutsch and J. D. Rogers, Pharmacokinetics of ertapenem in healthy young volunteers, ASM, 46 (2002), 3506–3511.
[11]	Merck & Co. Inc., Highlights of Prescribing Information, Invanz®(ertapenem for injection), 2012.
[12]	D. Nix, A. Majumdar and M. DiNubile, Pharmacokinetics and pharmacodynamics of ertapenem: an overview for clinicians, J. Antimicrob. Chemoth., 53 (2004), ii23–ii28.
[13]	S. Pilari and W. Huisinga, Lumping of physiologically-based pharmacokinetic models and a mechanistic derivation of classical compartmental models, J. Pharmacokinet. Phar., 37 (2010), 365–405.
[14]	D. Plowchalk and J. Teeguarden, Development of a physiologically based pharmacokinetic model for estradiol in rats and humans: A biologically motivated quantitative framework for evaluating responses to estradiol and other endocrine-active compounds, Toxicol. Sci., 69 (2002), 60–78.
[15]	P. Price, R. Conolly, C. Chaisson, E. Gross, J. Young, E. Mathis and D. Tedder, Modeling interindividual variation in physiological factors used in PBPK models of humans, Crit. Rev. Toxicol., 33 (2003), 469–503.
[16]	P. M. Shah and R. D. Isaacs, Ertapenem, the first of a new group of carbapenems, J. Antimicrob. Chemoth., 52 (2003), 538–542.
[17]	B. Tummers, DataThief iii, Available from: http://datathief.org/.

Reader Comments

Your name:*

Email:*
© 2019 the Author(s), licensee AIMS Press. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0)